Abstract
Human nuclear receptors (NRs) are a family of forty-eight transcription factors that modulate gene expression both spatially and temporally. Numerous biochemical, physiological, and pathological processes including cell survival, proliferation, differentiation, metabolism, immune modulation, development, reproduction, and aging are extensively orchestrated by different NRs. The involvement of dysregulated NRs and NR-mediated signaling pathways in driving cancer cell hallmarks has been thoroughly investigated. Targeting NRs has been one of the major focuses of drug development strategies for cancer interventions. Interestingly, rapid progress in molecular biology and drug screening reveals that the naturally occurring compounds are promising modern oncology drugs which are free of potentially inevitable repercussions that are associated with synthetic compounds. Therefore, the purpose of this review is to draw our attention to the potential therapeutic effects of various classes of natural compounds that target NRs such as phytochemicals, dietary components, venom constituents, royal jelly–derived compounds, and microbial derivatives in the establishment of novel and safe medications for cancer treatment. This review also emphasizes molecular mechanisms and signaling pathways that are leveraged to promote the anti-cancer effects of these natural compounds. We have also critically reviewed and assessed the advantages and limitations of current preclinical and clinical studies on this subject for cancer prophylaxis. This might subsequently pave the way for new paradigms in the discovery of drugs that target specific cancer types.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., et al. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71(3), 209–249, https://doi.org/10.3322/caac.21660.
Hanahan, D. (2022). Hallmarks of cancer: New dimensions. Cancer Discovery, 12(1), 31–46. https://doi.org/10.1158/2159-8290.CD-21-1059
Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: The next generation. Cell, 144(5), 646–674. https://doi.org/10.1016/j.cell.2011.02.013
Arora, L., Kumar, A. P., Arfuso, F., Chng, W. J., & Sethi, G. (2018). The role of signal transducer and activator of transcription 3 (STAT3) and its targeted inhibition in hematological malignancies. Cancers, 10(9), 327. https://doi.org/10.3390/cancers10090327
Bushweller, J. H. (2019). Targeting transcription factors in cancer - From undruggable to reality. Nature Reviews Cancer, 19(11), 611–624. https://doi.org/10.1038/s41568-019-0196-7
Garg, M., Shanmugam, M. K., Bhardwaj, V., Goel, A., Gupta, R., Sharma, A., et al. (2021). The pleiotropic role of transcription factor STAT3 in oncogenesis and its targeting through natural products for cancer prevention and therapy. Medicinal Research Reviews, 41(3), 1291–1336. https://doi.org/10.1002/med.21761
Mirzaei, S., Zarrabi, A., Hashemi, F., Zabolian, A., Saleki, H., Ranjbar, A., et al. (2021). Regulation of nuclear factor-kappaB (NF-κB) signaling pathway by non-coding RNAs in cancer: Inhibiting or promoting carcinogenesis? Cancer Letters, 509, 63–80. https://doi.org/10.1016/j.canlet.2021.03.025
Dhiman, V. K., Bolt, M. J., & White, K. P. (2018). Nuclear receptors in cancer—Uncovering new and evolving roles through genomic analysis. Nature Reviews Genetics, 19(3), 160–174. https://doi.org/10.1038/nrg.2017.102
Jayaprakash, S., Hegde, M., Girisa, S., Alqahtani, M. S., Abbas, M., Lee, E. H. C., et al. (2022). Demystifying the functional role of nuclear receptors in esophageal cancer. International Journal of Molecular Sciences, 23(18), 10952. https://doi.org/10.3390/ijms231810952.
Gangwar, S. K., Kumar, A., Jose, S., Alqahtani, M. S., Abbas, M., Sethi, G., et al. (2022). Nuclear receptors in oral cancer-Emerging players in tumorigenesis. Cancer Letters, 536, 215666. https://doi.org/10.1016/j.canlet.2022.215666
Gangwar, S. K., Kumar, A., Yap, K. C., Jose, S., Parama, D., Sethi, G., et al. (2022). Targeting nuclear receptors in lung cancer-Novel therapeutic prospects. Pharmaceuticals (Basel), 15(5), https://doi.org/10.3390/ph15050624.
Girisa, S., Rana, V., Parama, D., Dutta, U., & Kunnumakkara, A. B. (2021). Differential roles of farnesoid X receptor (FXR) in modulating apoptosis in cancer cells. Advances in Protein Chemistry and Structural Biology, 126, 63–90. https://doi.org/10.1016/bs.apcsb.2021.02.006
Girisa, S., Henamayee, S., Parama, D., Rana, V., Dutta, U., & Kunnumakkara, A. B. (2021). Targeting farnesoid X receptor (FXR) for developing novel therapeutics against cancer. Molecular Biomedecine, 2(1), 21. https://doi.org/10.1186/s43556-021-00035-2
Tang, Q., Chen, Y., Meyer, C., Geistlinger, T., Lupien, M., Wang, Q., et al. (2011). A comprehensive view of nuclear receptor cancer cistromes. Cancer Research, 71(22), 6940–6947. https://doi.org/10.1158/0008-5472.CAN-11-2091
Santagata, S., Thakkar, A., Ergonul, A., Wang, B., Woo, T., Hu, R., et al. (2014). Taxonomy of breast cancer based on normal cell phenotype predicts outcome. The Journal of Clinical Investigation, 124(2), 859–870. https://doi.org/10.1172/JCI70941
Font-Diaz, J., Jimenez-Panizo, A., Caelles, C., Vivanco, M. D., Perez, P., Aranda, A., et al. (2021). Nuclear receptors: Lipid and hormone sensors with essential roles in the control of cancer development. Seminars in Cancer Biology, 73, 58–75. https://doi.org/10.1016/j.semcancer.2020.12.007
Zhao, L., Zhou, S., & Gustafsson, J. -Å. (2019). Nuclear receptors: Recent drug discovery for cancer therapies. Endocrine Reviews, 40(5), 1207–1249.
Burris, T. P., Solt, L. A., Wang, Y., Crumbley, C., Banerjee, S., Griffett, K., et al. (2013). Nuclear receptors and their selective pharmacologic modulators. Pharmacological Reviews, 65(2), 710–778. https://doi.org/10.1124/pr.112.006833
Ishigami-Yuasa, M., & Kagechika, H. (2020). Chemical screening of nuclear receptor modulators. International Journal of Molecular Sciences, 21(15), 5512. https://doi.org/10.3390/ijms21155512
Knapp, P., Gardner, P. H., Raynor, D. K., Woolf, E., & McMillan, B. (2010). Perceived risk of tamoxifen side effects: A study of the use of absolute frequencies or frequency bands, with or without verbal descriptors. Patient Education and Counseling, 79(2), 267–271.
Pratheeshkumar, P., Sreekala, C., Zhang, Z., Budhraja, A., Ding, S., Son, Y.-O., et al. (2012). Cancer prevention with promising natural products: Mechanisms of action and molecular targets. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 12(10), 1159–1184.
Harsha, C., Banik, K., Bordoloi, D., & Kunnumakkara, A. B. (2017). Antiulcer properties of fruits and vegetables: A mechanism based perspective. Food and Chemical Toxicology, 108, 104–119.
Elkordy, A. A., Haj-Ahmad, R. R., Awaad, A. S., & Zaki, R. M. (2021). An overview on natural product drug formulations from conventional medicines to nanomedicines: Past, present and future. Journal of Drug Delivery Science and Technology, 63, 102459.
Kunnumakkara, A. B., Nair, A. S., Ahn, K. S., Pandey, M. K., Yi, Z., Liu, M., et al. (2007). Gossypin, a pentahydroxy glucosyl flavone, inhibits the transforming growth factor beta-activated kinase-1-mediated NF-kappaB activation pathway, leading to potentiation of apoptosis, suppression of invasion, and abrogation of osteoclastogenesis. Blood, 109(12), 5112–5121. https://doi.org/10.1182/blood-2007-01-067256
Muralimanoharan, S. B., Kunnumakkara, A. B., Shylesh, B., Kulkarni, K. H., Haiyan, X., Ming, H., et al. (2009). Butanol fraction containing berberine or related compound from nexrutine inhibits NFkappaB signaling and induces apoptosis in prostate cancer cells. Prostate, 69(5), 494–504. https://doi.org/10.1002/pros.20899
Kunnumakkara, A. B., Sung, B., Ravindran, J., Diagaradjane, P., Deorukhkar, A., Dey, S., et al. (2012). Zyflamend suppresses growth and sensitizes human pancreatic tumors to gemcitabine in an orthotopic mouse model through modulation of multiple targets. International Journal of Cancer, 131(3), E292-303. https://doi.org/10.1002/ijc.26442
Huang, M., Lu, J.-J., & Ding, J. (2021). Natural products in cancer therapy: Past, present and future. Natural Products and Bioprospecting, 11(1), 5–13.
Huang, M.-Y., Zhang, L.-L., Ding, J., & Lu, J.-J. (2018). Anticancer drug discovery from Chinese medicinal herbs. Chinese Medicine, 13(1), 1–9.
Newman, D. J., & Cragg, G. M. (2020). Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. Journal of Natural Products, 83(3), 770–803.
Liu, C., Ho, P.C.-L., Wong, F. C., Sethi, G., Wang, L. Z., & Goh, B. C. (2015). Garcinol: Current status of its anti-oxidative, anti-inflammatory and anti-cancer effects. Cancer Letters, 362(1), 8–14.
Kirtonia, A., Gala, K., Fernandes, S. G., Pandya, G., Pandey, A. K., Sethi, G., et al. Repurposing of drugs: An attractive pharmacological strategy for cancer therapeutics. In Seminars in Cancer Biology, 2021 (Vol. 68, pp. 258–278): Elsevier
Huang, P. X., Chandra, V., & Rastinejad, F. (2010). Structural overview of the nuclear receptor superfamily: Insights into physiology and therapeutics. Annual Review of Physiology, 72, 247–272. https://doi.org/10.1146/annurev-physiol-021909-135917
Papacleovoulou, G., Abu-Hayyeh, S., & Williamson, C. (2011). Nuclear receptor-driven alterations in bile acid and lipid metabolic pathways during gestation. Biochimica et Biophysica Acta, 1812(8), 879–887. https://doi.org/10.1016/j.bbadis.2010.11.001
Choi, J. M., & Bothwell, A. L. M. (2012). The nuclear receptor PPARs as important regulators of T-cell functions and autoimmune diseases. Molecules and Cells, 33(3), 217–222. https://doi.org/10.1007/s10059-012-2297-y
Nagy, Z. S., Czimmerer, Z., & Nagy, L. (2013). Nuclear receptor mediated mechanisms of macrophage cholesterol metabolism. Molecular and Cellular Endocrinology, 368(1–2), 85–98. https://doi.org/10.1016/j.mce.2012.04.003
Jin, Z., Li, X., & Wan, Y. (2015). Minireview: Nuclear receptor regulation of osteoclast and bone remodeling. Molecular Endocrinology, 29(2), 172–186. https://doi.org/10.1210/me.2014-1316
Yin, K., & Smith, A. G. (2016). Nuclear receptor function in skin health and disease: Therapeutic opportunities in the orphan and adopted receptor classes. Cellular and Molecular Life Sciences, 73(20), 3789–3800. https://doi.org/10.1007/s00018-016-2329-4
Makishima, M., Okamoto, A. Y., Repa, J. J., Tu, H., Learned, R. M., Luk, A., et al. (1999). Identification of a nuclear receptor for bile acids. Science, 284(5418), 1362–1365. https://doi.org/10.1126/science.284.5418.1362
Moore, L. B., Parks, D. J., Jones, S. A., Bledsoe, R. K., Consler, T. G., Stimmel, J. B., et al. (2000). Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands. Journal of Biological Chemistry, 275(20), 15122–15127. https://doi.org/10.1074/jbc.M001215200
Chawla, A., Repa, J. J., Evans, R. M., & Mangelsdorf, D. J. (2001). Nuclear receptors and lipid physiology: Opening the X-files. Science, 294(5548), 1866–1870. https://doi.org/10.1126/science.294.5548.1866
Orth, D. N., Kovacs, W., & DeBold, C. R. (1998). Williams textbook of endocrinology. In Williams Textbook of Endocrinology. WB Saunders Co.
Sporn, M. B., Roberts, A. B., & Goodman, D. S. (1994). The retinoids: Biology, chemistry, and medicine (pp. 319). Lippincott Williams & Wilkins.
Thummel, C. S. (1995). From embryogenesis to metamorphosis: The regulation and function of Drosophila nuclear receptor superfamily members. Cell, 83(6), 871–877. https://doi.org/10.1016/0092-8674(95)90203-1
Jones, G., Strugnell, S. A., & DeLuca, H. F. (1998). Current understanding of the molecular actions of vitamin D. Physiological Reviews, 78(4), 1193–1231. https://doi.org/10.1152/physrev.1998.78.4.1193
Forrest, D., & Vennstrom, B. (2000). Functions of thyroid hormone receptors in mice. Thyroid, 10(1), 41–52. https://doi.org/10.1089/thy.2000.10.41
Germain, P., Staels, B., Dacquet, C., Spedding, M., & Laudet, V. (2006). Overview of nomenclature of nuclear receptors. Pharmacological Reviews, 58(4), 685–704.
Helsen, C., & Claessens, F. (2014). Looking at nuclear receptors from a new angle. Molecular and Cellular Endocrinology, 382(1), 97–106. https://doi.org/10.1016/j.mce.2013.09.009
Weikum, E. R., Liu, X., & Ortlund, E. A. (2018). The nuclear receptor superfamily: A structural perspective. Protein Science, 27(11), 1876–1892.
Schwabe, J. W., Chapman, L., Finch, J. T., & Rhodes, D. (1993). The crystal structure of the estrogen receptor DNA-binding domain bound to DNA: How receptors discriminate between their response elements. Cell, 75(3), 567–578. https://doi.org/10.1016/0092-8674(93)90390-c
Zhang, J., Chalmers, M. J., Stayrook, K. R., Burris, L. L., Wang, Y., Busby, S. A., et al. (2011). DNA binding alters coactivator interaction surfaces of the intact VDR-RXR complex. Nature Structural & Molecular Biology, 18(5), 556–563. https://doi.org/10.1038/nsmb.2046
Yu, X., Yi, P., Hamilton, R. A., Shen, H., Chen, M., Foulds, C. E., et al. (2020). Structural insights of transcriptionally active, full-length androgen receptor coactivator complexes. Molecular Cell, 79(5), 812–823. e814.
Claessens, F., & Gewirth, D. T. (2004). DNA recognition by nuclear receptors. Essays in Biochemistry, 40, 59–72. https://doi.org/10.1042/bse0400059
Cotnoir-White, D., Laperrière, D., & Mader, S. (2011). Evolution of the repertoire of nuclear receptor binding sites in genomes. Molecular and Cellular Endocrinology, 334(1–2), 76–82.
Penvose, A., Keenan, J. L., Bray, D., Ramlall, V., & Siggers, T. (2019). Comprehensive study of nuclear receptor DNA binding provides a revised framework for understanding receptor specificity. Nature Communications, 10(1), 1–15.
Hong, H., Kohli, K., Trivedi, A., Johnson, D. L., & Stallcup, M. R. (1996). GRIP1, a novel mouse protein that serves as a transcriptional coactivator in yeast for the hormone binding domains of steroid receptors. Proceedings of the National Academy of Sciences, 93(10), 4948–4952.
Onate, S. A., Tsai, S. Y., Tsai, M. J., & O’Malley, B. W. (1995). Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science, 270(5240), 1354–1357. https://doi.org/10.1126/science.270.5240.1354
Kamei, Y., Xu, L., Heinzel, T., Torchia, J., Kurokawa, R., Gloss, B., et al. (1996). A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell, 85(3), 403–414.
Takeshita, A., Yen, P. M., Misiti, S., Cardona, G. R., Liu, Y., & Chin, W. W. (1996). Molecular cloning and properties of a full-length putative thyroid hormone receptor coactivator. Endocrinology, 137(8), 3594–3597.
Voegel, J. J., Heine, M., Zechel, C., Chambon, P., & Gronemeyer, H. (1996). TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors. The EMBO Journal, 15(14), 3667–3675.
Anzick, S. L., Kononen, J., Walker, R. L., Azorsa, D. O., Tanner, M. M., Guan, X.-Y., et al. (1997). AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science, 277(5328), 965–968.
Torchia, J., Rose, D. W., Inostroza, J., Kamei, Y., Westin, S., Glass, C. K., et al. (1997). The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function. Nature, 387(6634), 677–684.
McKenna, N. J., & O’Malley, B. W. (2002). Combinatorial control of gene expression by nuclear receptors and coregulators. Cell, 108(4), 465–474.
Chen, H., Lin, R. J., Schiltz, R. L., Chakravarti, D., Nash, A., Nagy, L., et al. (1997). Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell, 90(3), 569–580.
Yoshinaga, S. K., Peterson, C. L., Herskowitz, I., & Yamamoto, K. R. (1992). Roles of SWI1, SWI2, and SWI3 proteins for transcriptional enhancement by steroid receptors. Science, 258(5088), 1598–1604.
Chakravarti, D. (1996). LaMorte VJ, Nelson MC, Nakajima T, Schulman IG, Juguilon H, Montminy M, Evans RM. Role of CBP/P300 in nuclear receptor signalling. Nature, 383, 99–103.
Fondell, J. D., Ge, H., & Roeder, R. G. (1996). Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex. Proceedings National Academy of Sciences of the United States of America, 93(16), 8329–8333. https://doi.org/10.1073/pnas.93.16.8329
Fryer, C. J., & Archer, T. K. (1998). Chromatin remodelling by the glucocorticoid receptor requires the BRG1 complex. Nature, 393(6680), 88–91.
Rachez, C., Suldan, Z., Ward, J., Chang, C.-P.B., Burakov, D., Erdjument-Bromage, H., et al. (1998). A novel protein complex that interacts with the vitamin D3 receptor in a ligand-dependent manner and enhances VDR transactivation in a cell-free system. Genes & Development, 12(12), 1787–1800.
Chen, D. G., Ma, H., Hong, H., Koh, S. S., Huang, S. M., Schurter, B. T., et al. (1999). Regulation of transcription by a protein methyltransferase. Science, 284(5423), 2174–2177. https://doi.org/10.1126/science.284.5423.2174
Lanz, R. B., McKenna, N. J., Onate, S. A., Albrecht, U., Wong, J. M., Tsai, S. Y., et al. (1999). A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. Cell, 97(1), 17–27. https://doi.org/10.1016/S0092-8674(00)80711-4
Nawaz, Z., Lonard, D. M., Smith, C. L., Lev-Lehman, E., Tsai, S. Y., Tsai, M.-J., et al. (1999). The Angelman syndrome-associated protein, E6-AP, is a coactivator for the nuclear hormone receptor superfamily. Molecular and Cellular Biology, 19(2), 1182–1189. https://doi.org/10.1128/MCB.19.2.1182
Näär, A. M., Lemon, B. D., & Tjian, R. (2001). Transcriptional coactivator complexes. Annual Review of Biochemistry, 70(1), 475–501.
Wang, H. B., Huang, Z. Q., Xia, L., Feng, Q., Erdjument-Bromage, H., Strahl, B. D., et al. (2001). Methylation of histone H4 at arginine 3 facilitating transcriptional activation by nuclear hormone receptor. Science, 293(5531), 853–857. https://doi.org/10.1126/science.1060781
Heery, D. M., Kalkhoven, E., Hoare, S., & Parker, M. G. (1997). A signature motif in transcriptional co-activators mediates binding to nuclear receptors. Nature, 387(6634), 733–736. https://doi.org/10.1038/42750
Bannister, A. J., & Kouzarides, T. (1996). The CBP co-activator is a histone acetyltransferase. Nature, 384(6610), 641–643. https://doi.org/10.1038/384641a0
Yang, X. J., Ogryzko, V. V., Nishikawa, J., Howard, B. H., & Nakatani, Y. (1996). A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A. Nature, 382(6589), 319–324. https://doi.org/10.1038/382319a0
Spencer, T. E., Jenster, G., Burcin, M. M., Allis, C. D., Zhou, J. X., Mizzen, C. A., et al. (1997). Steroid receptor coactivator-1 is a histone acetyltransferase. Nature, 389(6647), 194–198. https://doi.org/10.1038/38304
Chen, J. D., & Evans, R. M. (1995). A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature, 377(6548), 454–457. https://doi.org/10.1038/377454a0
Horlein, A. J., Naar, A. M., Heinzel, T., Torchia, J., Gloss, B., Kurokawa, R., et al. (1995). Ligand-independent repression by the thyroid-hormone receptor-mediated by a nuclear receptor co-repressor. Nature, 377(6548), 397–404. https://doi.org/10.1038/377397a0
Hu, X., & Lazar, M. A. (1999). The CoRNR motif controls the recruitment of corepressors by nuclear hormone receptors. Nature, 402(6757), 93–96. https://doi.org/10.1038/47069
Cavailles, V., Dauvois, S., Lhorset, F., Lopez, G., Hoare, S., Kushner, P. J., et al. (1995). Nuclear factor Rip140 modulates transcriptional activation by the estrogen-receptor. The EMBO Journal, 14(15), 3741–3751. https://doi.org/10.1002/j.1460-2075.1995.tb00044.x
Windahl, S. H., Treuter, E., Ford, J., Zilliacus, J., Gustafsson, J. A., & McEwan, I. J. (1999). The nuclear-receptor interacting protein (RIP) 140 binds to the human glucocorticoid receptor and modulates hormone-dependent transactivation. Journal of Steroid Biochemistry and Molecular Biology, 71(3–4), 93–102. https://doi.org/10.1016/S0960-0760(99)00128-4
Sever, R., & Glass, C. K. (2013). Signaling by nuclear receptors. Cold Spring Harbor Perspectives in Biology, 5(3), a016709. https://doi.org/10.1101/cshperspect.a016709
Ong, P. S., Wang, L. Z., Dai, X., Tseng, S. H., Loo, S. J., & Sethi, G. (2016). Judicious toggling of mTOR activity to combat insulin resistance and cancer: Current evidence and perspectives. Frontiers in Pharmacology, 7, 395.
Dai, Y., Qiao, L., Chan, K. W., Yang, M., Ye, J. Y., Ma, J., et al. (2009). Peroxisome proliferator-activated receptor-gamma contributes to the inhibitory effects of embelin on colon carcinogenesis. Cancer Research, 69(11), 4776–4783. https://doi.org/10.1158/0008-5472.Can-08-4754
Ramachandran, L., Manu, K. A., Shanmugam, M. K., Li, F., Siveen, K. S., Vali, S., et al. (2012). Isorhamnetin inhibits proliferation and invasion and induces apoptosis through the modulation of peroxisome proliferator-activated receptor γ activation pathway in gastric cancer. Journal of Biological Chemistry, 287(45), 38028–38040.
Sikka, S., Chen, L., Sethi, G., & Kumar, A. P. (2012). Targeting PPARγ signaling cascade for the prevention and treatment of prostate cancer. PPAR Research, 2012, 968040.
Zhang, J., Ahn, K. S., Kim, C., Shanmugam, M. K., Siveen, K. S., Arfuso, F., et al. (2016). Nimbolide-induced oxidative stress abrogates STAT3 signaling cascade and inhibits tumor growth in transgenic adenocarcinoma of mouse prostate model. Antioxidants & Redox Signaling, 24(11), 575–589.
Raghunath, A., Sundarraj, K., Arfuso, F., Sethi, G., & Perumal, E. (2018). Dysregulation of Nrf2 in hepatocellular carcinoma: Role in cancer progression and chemoresistance. Cancers, 10(12), 481.
Duez, H., & Pourcet, B. (2021). Nuclear receptors in the control of the NLRP3 inflammasome pathway. Frontiers in Endocrinology, 12, 630536.
Alatshan, A., & Benkő, S. (2021). Nuclear receptors as multiple regulators of nlrp3 inflammasome function. Frontiers in Immunology, 12, 630569.
Whyte-Allman, S.-K., Hoque, M. T., Jenabian, M.-A., Routy, J.-P., & Bendayan, R. (2017). Xenobiotic nuclear receptors pregnane X receptor and constitutive androstane receptor regulate antiretroviral drug efflux transporters at the blood-testis barrier. Journal of Pharmacology and Experimental Therapeutics, 363(3), 324–335.
Lemmen, J., Tozakidis, I. E., Bele, P., & Galla, H.-J. (2013). Constitutive androstane receptor upregulates Abcb1 and Abcg2 at the blood–brain barrier after CITCO activation. Brain Research, 1501, 68–80.
Jigorel, E., Le Vee, M., Boursier-Neyret, C., Parmentier, Y., & Fardel, O. (2006). Differential regulation of sinusoidal and canalicular hepatic drug transporter expression by xenobiotics activating drug-sensing receptors in primary human hepatocytes. Drug Metabolism and Disposition, 34(10), 1756–1763.
Chisaki, I., Kobayashi, M., Itagaki, S., Hirano, T., & Iseki, K. (2009). Liver X receptor regulates expression of MRP2 but not that of MDR1 and BCRP in the liver. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1788(11), 2396–2403.
Chen, T. (2010). Overcoming drug resistance by regulating nuclear receptors. Advanced Drug Delivery Reviews, 62(13), 1257–1264.
Geick, A., Eichelbaum, M., & Burk, O. (2001). Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. Journal of Biological Chemistry, 276(18), 14581–14587. https://doi.org/10.1074/jbc.M010173200
Cerveny, L., Svecova, L., Anzenbacherova, E., Vrzal, R., Staud, F., Dvorak, Z., et al. (2007). Valproic acid induces CYP3A4 and MDR1 gene expression by activation of constitutive androstane receptor and pregnane X receptor pathways. Drug Metabolism and Disposition, 35(7), 1032–1041.
Ee, P. L. R., Kamalakaran, S., Tonetti, D., He, X., Ross, D. D., & Beck, W. T. (2004). Identification of a novel estrogen response element in the breast cancer resistance protein (ABCG2) gene. Cancer research, 64(4), 1247–1251.
Szatmari, I., Vámosi, G. r., Brazda, P., Balint, B. L., Benko, S., Széles, L., et al. (2006). Peroxisome proliferator-activated receptor γ-regulated ABCG2 expression confers cytoprotection to human dendritic cells. Journal of Biological Chemistry, 281(33), 23812-23823.
Burk, O., Arnold, K. A., Geick, A., Tegude, H., & Eichelbaum, M. (2005). A role for constitutive androstane receptor in the regulation of human intestinal MDR1 expression. Biological Chemistry, 86(6), 503–513. https://doi.org/10.1515/BC.2005.060
Cao, D., Qi, Z., Pang, Y., Li, H., Xie, H., Wu, J., et al. (2019). Retinoic acid-related orphan receptor c regulates proliferation, glycolysis, and chemoresistance via the PD-L1/ITGB6/STAT3 signaling axis in bladder cancer. Cancer Research, 79(10), 2604–2618. https://doi.org/10.1158/0008-5472.CAN-18-3842
Hu, L., Sun, Y., Luo, J., He, X., Ye, M., Li, G., et al. (2020). Targeting TR4 nuclear receptor with antagonist bexarotene increases docetaxel sensitivity to better suppress the metastatic castration-resistant prostate cancer progression. Oncogene, 39(9), 1891–1903.
Kai, L., & Levenson, A. S. (2011). Combination of resveratrol and antiandrogen flutamide has synergistic effect on androgen receptor inhibition in prostate cancer cells. Anticancer Research, 31(10), 3323–3330.
Penson, D. F., Armstrong, A. J., Concepcion, R., Agarwal, N., Olsson, C., Karsh, L., et al. (2016). Enzalutamide versus bicalutamide in castration-resistant prostate cancer: The STRIVE Trial. Journal of Clinical Oncology, 34(18), 2098–2106. https://doi.org/10.1200/JCO.2015.64.9285
de Bono, J. S., Chowdhury, S., Feyerabend, S., Elliott, T., Grande, E., Melhem-Bertrandt, A., et al. (2018). Antitumour activity and safety of enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with abiraterone acetate plus prednisone for >= 24 weeks in Europe. European Urology, 74(1), 37–45. https://doi.org/10.1016/j.eururo.2017.07.035
Lee, H. Y., Chen, H. L., Teoh, J. Y. C., Chen, T. C., Hao, S. Y., Tsai, H. Y., et al. (2021). Abiraterone and enzalutamide had different adverse effects on the cardiovascular system: A systematic review with pairwise and network meta-analyses. Prostate Cancer and Prostatic Diseases, 24(1), 244–252. https://doi.org/10.1038/s41391-020-00275-3
Johnson, D. B., & Sonthalia, S. (2022). Flutamide. In StatPearls. StatPearls Publishing.
Argnani, L., Broccoli, A., & Zinzani, P. L. (2017). Cutaneous T-cell lymphomas: Focusing on novel agents in relapsed and refractory disease. Cancer Treatment Reviews, 61, 61–69. https://doi.org/10.1016/j.ctrv.2017.10.007
Binkhorst, L., Mathijssen, R. H. J., Jager, A., & van Gelder, T. (2015). Individualization of tamoxifen therapy: Much more than just CYP2D6 genotyping. Cancer Treatment Reviews, 41(3), 289–299. https://doi.org/10.1016/j.ctrv.2015.01.002
Culig, Z. (2014). Targeting the androgen receptor in prostate cancer. Expert Opinion on Pharmacotherapy, 15(10), 1427–1437.
de The, H., Pandolfi, P. P., & Chen, Z. (2017). Acute promyelocytic leukemia: A paradigm for oncoprotein-targeted cure. Cancer Cell, 32(5), 552–560. https://doi.org/10.1016/j.ccell.2017.10.002
Facciola, A., Venanzi Rullo, E., Ceccarelli, M., D'Aleo, F., Di Rosa, M., Pinzone, M. R., et al. (2017). Kaposi’s sarcoma in HIV-infected patients in the era of new antiretrovirals.European Review for Medical Pharmacological Sciences, 21(24), 5868–5869, https://doi.org/10.26355/eurrev_201712_14036.
Gniadecki, R., Assaf, C., Bagot, M., Dummer, R., Duvic, M., Knobler, R., et al. (2007). The optimal use of bexarotene in cutaneous T-cell lymphoma. British Journal of Dermatology, 157(3), 433–440. https://doi.org/10.1111/j.1365-2133.2007.07975.x
Jordan, V. C. (2014). Tamoxifen as the first targeted long-term adjuvant therapy for breast cancer. Endocrine-Related Cancer, 21(3), R235–R246. https://doi.org/10.1530/Erc-14-0092
McKeage, K., Curran, M. P., & Plosker, G. L. (2004). Fulvestrant. Drugs, 64(6), 633–648.
Nathan, M. R., & Schmid, P. (2017). A review of fulvestrant in breast cancer. Oncology and Therapy, 5(1), 17–29.
Pileri, A., Delfino, C., Grandi, V., & Pimpinelli, N. (2013). Role of bexarotene in the treatment of cutaneous T-cell lymphoma: The clinical and immunological sides. Immunotherapy, 5(4), 427–433. https://doi.org/10.2217/Imt.13.15
Rathkopf, D. E., Beer, T. M., Loriot, Y., Higano, C. S., Armstrong, A. J., Sternberg, C. N., et al. (2018). Radiographic progression-free survival as a clinically meaningful end point in metastatic castration-resistant prostate cancer: The PREVAIL Randomized Clinical Trial. Jama Oncology, 4(5), 694–701. https://doi.org/10.1001/jamaoncol.2017.5808
Rathkopf, D. E., Smith, M., Ryan, C., Berry, W., Shore, N., Liu, G., et al. (2017). Androgen receptor mutations in patients with castration-resistant prostate cancer treated with apalutamide. Annals of Oncology, 28(9), 2264–2271.
Scott, S. M., Brown, M., & Come, S. E. (2011). Emerging data on the efficacy and safety of fulvestrant, a unique antiestrogen therapy for advanced breast cancer. Expert Opinion on Drug Safety, 10(5), 819–826. https://doi.org/10.1517/14740338.2011.595560
Smith, M. R., Antonarakis, E. S., Ryan, C. J., Berry, W. R., Shore, N. D., Liu, G., et al. (2016). Phase 2 study of the safety and antitumor activity of apalutamide (ARN-509), a potent androgen receptor antagonist, in the high-risk nonmetastatic castration-resistant prostate cancer cohort. European Urology, 70(6), 963–970.
Smith, M. R., Saad, F., Chowdhury, S., Oudard, S., Hadaschik, B. A., Graff, J. N., et al. (2018). Apalutamide treatment and metastasis-free survival in prostate cancer. New England Journal of Medicine, 378(15), 1408–1418.
Vogel, C. L., Johnston, M. A., Capers, C., & Braccia, D. (2014). Toremifene for breast cancer: A review of 20 years of data. Clinical Breast Cancer, 14(1), 1–9. https://doi.org/10.1016/j.clbc.2013.10.014
Wiseman, L. R., & Goa, K. L. (1997). Toremifene. Drugs, 54(1), 141–160.
Warrell, R. P., Jr., Frankel, S. R., Miller, W. H., Jr., Scheinberg, D. A., Itri, L. M., Hittelman, W. N., et al. (1991). Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid). New England Journal of Medicine, 324(20), 1385–1393. https://doi.org/10.1056/NEJM199105163242002
Wong, Y. N. S., Ferraldeschi, R., Attard, G., & de Bono, J. (2014). Evolution of androgen receptor targeted therapy for advanced prostate cancer. Nature Reviews Clinical Oncology, 11(6), 365–376. https://doi.org/10.1038/nrclinonc.2014.72
Wu, P. A., & Stern, R. S. (2012). Topical tretinoin, another failure in the pursuit of practical chemoprevention for non-melanoma skin cancer. Journal of Investigative Dermatology, 132(6), 1532–1535.
Quinn, B. J., Dallos, M., Kitagawa, H., Kunnumakkara, A. B., Memmott, R. M., Hollander, M. C., et al. (2013). Inhibition of lung tumorigenesis by metformin is associated with decreased plasma IGF-I and diminished receptor tyrosine kinase signaling. Cancer Prevention Research (Philadelphia, Pa.), 6(8), 801–810. https://doi.org/10.1158/1940-6207.CAPR-13-0058-T
Parama, D., Boruah, M., Yachna, K., Rana, V., Banik, K., Harsha, C., et al. (2020). Diosgenin, a steroidal saponin, and its analogs: Effective therapies against different chronic diseases. Life Sciences, 260, 118182. https://doi.org/10.1016/j.lfs.2020.118182
Kunnumakkara, A. B., Banik, K., Bordoloi, D., Harsha, C., Sailo, B. L., Padmavathi, G., et al. (2018). Googling the guggul (Commiphora and Boswellia) for prevention of chronic diseases. Frontiers in Pharmacology, 9, 686. https://doi.org/10.3389/fphar.2018.00686
Babu, B. H., Jayram, H. N., Nair, M. G., Ajaikumar, K. B., & Padikkala, J. (2003). Free radical scavenging, antitumor and anticarcinogenic activity of gossypin. Journal of Experimental & Clinical Cancer Research, 22(4), 581–589.
Padmavathi, G., Rathnakaram, S. R., Monisha, J., Bordoloi, D., Roy, N. K., & Kunnumakkara, A. B. (2015). Potential of butein, a tetrahydroxychalcone to obliterate cancer. Phytomedicine, 22(13), 1163–1171. https://doi.org/10.1016/j.phymed.2015.08.015
Henamayee, S., Banik, K., Sailo, B. L., Shabnam, B., Harsha, C., Srilakshmi, S., et al. (2020). Therapeutic emergence of rhein as a potential anticancer drug: A review of its molecular targets and anticancer properties. Molecules, 25(10), 2278. https://doi.org/10.3390/molecules25102278
Heymach, J. V., Shackleford, T. J., Tran, H. T., Yoo, S. Y., Do, K. A., Wergin, M., et al. (2011). Effect of low-fat diets on plasma levels of NF-kappaB-regulated inflammatory cytokines and angiogenic factors in men with prostate cancer. Cancer Prevention Research (Philadelphia, Pa.), 4(10), 1590–1598. https://doi.org/10.1158/1940-6207.CAPR-10-0136
Khatoon, E., Banik, K., Harsha, C., Sailo, B. L., Thakur, K. K., Khwairakpam, A. D., et al. (2022). Phytochemicals in cancer cell chemosensitization: Current knowledge and future perspectives. Seminars in Cancer Biology, 80, 306–339. https://doi.org/10.1016/j.semcancer.2020.06.014
Kunnumakkara, A. B., Koca, C., Dey, S., Gehlot, P., Yodkeeree, S., Danda, D., et al. (2009). Traditional uses of spices: An overview. Molecular Targets and Therapeutic Uses of Spices: Modern Uses for Ancient Medicine, 1–24. https://doi.org/10.1142/9789812837912_0001
Kunnumakkara, A. B., Bordoloi, D., Sailo, B. L., Roy, N. K., Thakur, K. K., Banik, K., et al. (2019). Cancer drug development: The missing links. Experimental Biology and Medicine (Maywood, N.J.), 244(8), 663–689. https://doi.org/10.1177/1535370219839163
Delfosse, V., Maire, A. I., Balaguer, P., & Bourguet, W. (2015). A structural perspective on nuclear receptors as targets of environmental compounds. Acta Pharmacologica Sinica, 36(1), 88–101.
Manu, K. A., Shanmugam, M. K., Li, F., Chen, L., Siveen, K. S., Ahn, K. S., et al. (2014). Simvastatin sensitizes human gastric cancer xenograft in nude mice to capecitabine by suppressing nuclear factor-kappa B-regulated gene products. Journal of Molecular Medicine, 92(3), 267–276.
Hsieh, Y.-S., Yang, S.-F., Sethi, G., & Hu, D.-N. (2015). Natural bioactives in cancer treatment and prevention. BioMed Research International, 2015, 182835. https://doi.org/10.1155/2015/182835
Patel, S. M., Venkata, K. C. N., Bhattacharyya, P., Sethi, G., & Bishayee, A. Potential of neem (Azadirachta indica L.) for prevention and treatment of oncologic diseases. In Seminars in Cancer Biology, 2016 (Vol. 40, pp. 100–115): Elsevier
Kim, C., Lee, S.-G., Yang, W. M., Arfuso, F., Um, J.-Y., Kumar, A. P., et al. (2018). Formononetin-induced oxidative stress abrogates the activation of STAT3/5 signaling axis and suppresses the tumor growth in multiple myeloma preclinical model. Cancer Letters, 431, 123–141.
Benyhe, S. (1994). Morphine: New aspects in the study of an ancient compound. Life Sciences, 55(13), 969–979. https://doi.org/10.1016/0024-3205(94)00631-8
Mondal, A., Gandhi, A., Fimognari, C., Atanasov, A. G., & Bishayee, A. (2019). Alkaloids for cancer prevention and therapy: Current progress and future perspectives. European Journal of Pharmacology, 858, 172472. https://doi.org/10.1016/j.ejphar.2019.172472
Huang, M., Gao, H., Chen, Y., Zhu, H., Cai, Y., Zhang, X., et al. (2007). Chimmitecan, a novel 9-substituted camptothecin, with improved anticancer pharmacologic profiles in vitro and in vivo. Clinical Cancer Research, 13(4), 1298–1307. https://doi.org/10.1158/1078-0432.CCR-06-1277
Li, W., Shao, Y., Hu, L., Zhang, X., Chen, Y., Tong, L., et al. (2007). BM6, a new semi-synthetic vinca alkaloid, exhibits its potent in vivo anti-tumor activities via its high binding affinity for tubulin and improved pharmacokinetic profiles. Cancer Biology & Therapy, 6(5), 787–794. https://doi.org/10.4161/cbt.6.5.4006
Habtemariam, S. (2016). Berberine and inflammatory bowel disease: A concise review. Pharmacological Research, 113(Pt A), 592–599. https://doi.org/10.1016/j.phrs.2016.09.041
Ruan, H., Zhan, Y. Y., Hou, J., Xu, B., Chen, B., Tian, Y., et al. (2017). Berberine binds RXRalpha to suppress beta-catenin signaling in colon cancer cells. Oncogene, 36(50), 6906–6918. https://doi.org/10.1038/onc.2017.296
Cancer, I. A. f. R. o. (1991). Coffee, tea, mate, methylxanthines, and methyglyoxal. IARC Monograph on the Evaluation of Carcinogenic Risk of Chemicals to Humans, 51, 1–513.
Tolmach, L. J., Jones, R. W., & Busse, P. M. (1977). The action of caffeine on X-irradiated HeLa cells. I. Delayed inhibition of DNA synthesis. Radiation Research, 71(3), 653–665.
Busse, P. M., Bose, S. K., Jones, R. W., & Tolmach, L. J. (1978). The action of caffeine on X-irradiated HeLa cells. III. Enhancement of X-ray-induced killing during G2 arrest. Radiation Research, 76(2), 292–307.
Lau, C. C., & Pardee, A. B. (1982). Mechanism by which caffeine potentiates lethality of nitrogen-mustard. Proceedings of the National Academy of Sciences of the United States of America-Biological Sciences, 79(9), 2942–2946. https://doi.org/10.1073/pnas.79.9.2942
Levi-Schaffer, F., & Touitou, E. (1991). Xanthines inhibit 3T3 fibroblast proliferation. Skin Pharmacology, 4(4), 286–290. https://doi.org/10.1159/000210963
Lou, Y. R., Lu, Y. P., Xie, J. G., Huang, M. T., & Conney, A. H. (1999). Effects of oral administration of tea, decaffeinated tea, and caffeine on the formation and growth of tumors in high-risk SKH-1 mice previously treated with ultraviolet B light. Nutrition and Cancer, 33(2), 146–153. https://doi.org/10.1207/S15327914NC330205
Nomura, M., Ichimatsu, D., Moritani, S., Koyama, I., Dong, Z., Yokogawa, K., et al. (2005). Inhibition of epidermal growth factor-induced cell transformation and Akt activation by caffeine. Molecular Carcinogenesis, 44(1), 67–76. https://doi.org/10.1002/mc.20120
Faudone, G., Kilu, W., Ni, X., Chaikuad, A., Sreeramulu, S., Heitel, P., et al. (2021). The transcriptional repressor orphan nuclear receptor TLX is responsive to xanthines. ACS Pharmacology & Translational Science, 4(6), 1794–1807.
Clark, R., & Lee, S. H. (2016). Anticancer properties of capsaicin against human cancer. Anticancer Research, 36(3), 837–843.
Kim, C. S., Park, W. H., Park, J. Y., Kang, J. H., Kim, M. O., Kawada, T., et al. (2004). Capsaicin, a spicy component of hot pepper, induces apoptosis by activation of the peroxisome proliferator-activated receptor gamma in HT-29 human colon cancer cells. Journal of Medicinal Food, 7(3), 267–273. https://doi.org/10.1089/1096620041938713
Bort, A., Sanchez, B. G., Mateos-Gomez, P. A., Diaz-Laviada, I., & Rodriguez-Henche, N. (2019). Capsaicin targets lipogenesis in HepG2 cells through AMPK activation, AKT inhibition and PPARs regulation. International Journal of Molecular Sciences, 20(7), ARTN 1660. https://doi.org/10.3390/ijms20071660.
Kumar, S., Kamboj, J., & Sharma, S. (2011). Overview for various aspects of the health benefits of Piper longum linn. fruit. Journal of Acupuncture and Meridian Studies, 4(2), 134–140.
Zadorozhna, M., Tataranni, T., & Mangieri, D. (2019). Piperine: Role in prevention and progression of cancer. Molecular Biology Reports, 46(5), 5617–5629. https://doi.org/10.1007/s11033-019-04927-z
Rajarajan, D., Natesh, J., Penta, D., & Meeran, S. M. (2021). Dietary piperine suppresses obesity-associated breast cancer growth and metastasis by regulating the miR-181c-3p/PPARalpha axis. Journal of Agriculture and Food Chemistry, 69(51), 15562–15574. https://doi.org/10.1021/acs.jafc.1c05670
Vershinin, A. (1999). Biological functions of carotenoids - Diversity and evolution. BioFactors, 10(2–3), 99–104.
Sandmann, G. (2021). Diversity and evolution of carotenoid biosynthesis from prokaryotes to plants. Carotenoids: Biosynthetic and Biofunctional Approaches, 1261, 79–94. https://doi.org/10.1007/978-981-15-7360-6_7
Zare, M., Norouzi Roshan, Z., Assadpour, E., & Jafari, S. M. (2021). Improving the cancer prevention/treatment role of carotenoids through various nano-delivery systems. Critical Reviews in Food Science and Nutrition, 61(3), 522–534.
Zhang, X., Zhao, W.-E., Hu, L., Zhao, L., & Huang, J. (2011). Carotenoids inhibit proliferation and regulate expression of peroxisome proliferators-activated receptor gamma (PPARγ) in K562 cancer cells. Archives of Biochemistry and Biophysics, 512(1), 96–106.
Liu, C.-L., Lim, Y.-P., & Hu, M.-L. (2012). Fucoxanthin attenuates rifampin-induced cytochrome P450 3A4 (CYP3A4) and multiple drug resistance 1 (MDR1) gene expression through pregnane X receptor (PXR)-mediated pathways in human hepatoma HepG2 and colon adenocarcinoma LS174T cells. Marine Drugs, 10(1), 242–257.
Hosokawa, M., Kudo, M., Maeda, H., Kohno, H., Tanaka, T., & Miyashita, K. (2004). Fucoxanthin induces apoptosis and enhances the antiproliferative effect of the PPARγ ligand, troglitazone, on colon cancer cells. Biochimica et Biophysica Acta (BBA)-General Subjects, 1675(1–3), 113–119.
Lian, F., Hu, K. Q., Russell, R. M., & Wang, X. D. (2006). β-Cryptoxanthin suppresses the growth of immortalized human bronchial epithelial cells and non-small-cell lung cancer cells and up-regulates retinoic acid receptor β expression. International Journal of Cancer, 119(9), 2084–2089.
Iskandar, A. R., Liu, C., Smith, D. E., Hu, K.-Q., Choi, S.-W., Ausman, L. M., et al. (2013). β-Cryptoxanthin restores nicotine-reduced lung SIRT1 to normal levels and inhibits nicotine-promoted lung tumorigenesis and emphysema in A/J mice. Cancer Prevention Research, 6(4), 309–320.
Cheng, J., Miao, B., Hu, K.-Q., Fu, X., & Wang, X.-D. (2018). Apo-10’-lycopenoic acid inhibits cancer cell migration and angiogenesis and induces peroxisome proliferator-activated receptor γ. The Journal of Nutritional Biochemistry, 56, 26–34.
Manach, C., Scalbert, A., Morand, C., Rémésy, C., & Jiménez, L. (2004). Polyphenols: Food sources and bioavailability. The American journal of Clinical Nutrition, 79(5), 727–747.
Neveu, V., Perez-Jimenez, J., Vos, F., Crespy, V., du Chaffaut, L., Mennen, L., et al. (2010). Phenol-Explorer: An online comprehensive database on polyphenol contents in foods. Database (Oxford), 2010, bap024. https://doi.org/10.1093/database/bap024
Zhou, Y., Zheng, J., Li, Y., Xu, D.-P., Li, S., Chen, Y.-M., et al. (2016). Natural polyphenols for prevention and treatment of cancer. Nutrients, 8(8), 515.
Kausar, H., Jeyabalan, J., Aqil, F., Chabba, D., Sidana, J., Singh, I. P., et al. (2012). Berry anthocyanidins synergistically suppress growth and invasive potential of human non-small-cell lung cancer cells. Cancer Letters, 325(1), 54–62. https://doi.org/10.1016/j.canlet.2012.05.029
Wang, H., Zhang, H., Tang, L., Chen, H., Wu, C., Zhao, M., et al. (2013). Resveratrol inhibits TGF-beta1-induced epithelial-to-mesenchymal transition and suppresses lung cancer invasion and metastasis. Toxicology, 303, 139–146. https://doi.org/10.1016/j.tox.2012.09.017
Li, A. N., Li, S., Zhang, Y. J., Xu, X. R., Chen, Y. M., & Li, H. B. (2014). Resources and biological activities of natural polyphenols. Nutrients, 6(12), 6020–6047. https://doi.org/10.3390/nu6126020
Shi, W. F., Leong, M., Cho, E., Farrell, J., Chen, H. C., Tian, J., et al. (2009). Repressive effects of resveratrol on androgen receptor transcriptional activity. Plos One, 4(10), ARTN e7398. https://doi.org/10.1371/journal.pone.0007398.
Rigalli, J. P., Tocchetti, G. N., Arana, M. R., Villanueva, S. S., Catania, V. A., Theile, D., et al. (2016). The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters. Cancer Letters, 376(1), 165–172. https://doi.org/10.1016/j.canlet.2016.03.040
Kretschmer, N., Rinner, B., Deutsch, A. J. A., Lohberger, B., Knausz, H., Kunert, O., et al. (2012). Naphthoquinones from Onosma paniculata induce cell-cycle arrest and apoptosis in melanoma cells. Journal of Natural Products, 75(5), 865–869. https://doi.org/10.1021/np2006499
Park, S. H., Phuc, N. M., Lee, J., Wu, Z., Kim, J., Kim, H., et al. (2017). Identification of acetylshikonin as the novel CYP2J2 inhibitor with anti-cancer activity in HepG2 cells. Phytomedicine, 24, 134–140. https://doi.org/10.1016/j.phymed.2016.12.001
Liu, J., Zhou, W., Li, S. S., Sun, Z., Lin, B. Z., Lang, Y. Y., et al. (2008). Modulation of orphan nuclear receptor Nur77-mediated apoptotic pathway by acetylshikonin and analogues. Cancer Research, 68(21), 8871–8880. https://doi.org/10.1158/0008-5472.Can-08-1972
Moon, J., Koh, S. S., Malilas, W., Cho, I. R., Kaewpiboon, C., Kaowinn, S., et al. (2014). Acetylshikonin induces apoptosis of hepatitis B virus X protein-expressing human hepatocellular carcinoma cells via endoplasmic reticulum stress. European Journal of Pharmacology, 735, 132–140. https://doi.org/10.1016/j.ejphar.2014.04.021
Lai, H. C., Singh, N. P., & Sasaki, T. (2013). Development of artemisinin compounds for cancer treatment. Investigational New Drugs, 31(1), 230–246. https://doi.org/10.1007/s10637-012-9873-z
Steely, A. M., Willoughby, J. A., Sr., Sundar, S. N., Aivaliotis, V. I., & Firestone, G. L. (2017). Artemisinin disrupts androgen responsiveness of human prostate cancer cells by stimulating the 26S proteasome-mediated degradation of the androgen receptor protein. Anti-Cancer Drugs, 28(9), 1018–1031. https://doi.org/10.1097/CAD.0000000000000547
Morrissey, C., Gallis, B., Solazzi, J. W., Kim, B. J., Gulati, R., Vakar-Lopez, F., et al. (2010). Effect of artemisinin derivatives on apoptosis and cell cycle in prostate cancer cells. Anti-Cancer Drugs, 21(4), 423–432. https://doi.org/10.1097/CAD.0b013e328336f57b
Wang, Z. Z., Wang, C., Wu, Z. Y., Xue, J., Shen, B. X., Zuo, W., et al. (2017). Artesunate suppresses the growth of prostatic cancer cells through inhibiting androgen receptor. Biological & Pharmaceutical Bulletin, 40(4), 479–485. https://doi.org/10.1248/bpb.b16-00908
Lu, Z.-H., Peng, J.-H., Zhang, R.-X., Wang, F., Sun, H.-P., Fang, Y.-J., et al. (2018). Dihydroartemisinin inhibits colon cancer cell viability by inducing apoptosis through up-regulation of PPARγ expression. Saudi Journal of Biological Sciences, 25(2), 372–376.
Tayarani-Najaran, Z., Tayarani-Najaran, N., & Eghbali, S. (2021). A review of auraptene as an anticancer agent. Frontiers in Pharmacology, 12, 698352. https://doi.org/10.3389/fphar.2021.698352
Kawabata, K., Murakami, A., & Ohigashi, H. (2006). Auraptene decreases the activity of matrix metalloproteinases in dextran sulfate sodium-induced ulcerative colitis in ICR mice. Bioscience Biotechnology and Biochemistry, 70(12), 3062–3065. https://doi.org/10.1271/bbb.60393
Takahashi, N., Kang, M.-S., Kuroyanagi, K., Goto, T., Hirai, S., Ohyama, K., et al. (2008). Auraptene, a citrus fruit compound, regulates gene expression as a PPARα agonist in HepG2 hepatocytes. BioFactors, 33(1), 25–32.
Jamialahmadi, K., Salari, S., Alamolhodaei, N. S., Avan, A., Gholami, L., & Karimi, G. (2018). Auraptene inhibits migration and invasion of cervical and ovarian cancer cells by repression of matrix metalloproteinasas 2 and 9 activity. Journal of Pharmacopuncture, 21(3), 177–184. https://doi.org/10.3831/KPI.2018.21.021
Charmforoshan, E., Karimi, E., Oskoueian, E., Es-Haghi, A., & Iranshahi, M. (2019). Inhibition of human breast cancer cells (MCF-7 cell line) growth via cell proliferation, migration, and angiogenesis by auraptene of Ferula szowitsiana root extract. Journal of Food Measurement and Characterization, 13(4), 2644–2653. https://doi.org/10.1007/s11694-019-00185-6
Guo, Z. X., Hu, X. L., Xing, Z. Q., Xing, R., Lv, R. G., Cheng, X. Y., et al. (2015). Baicalein inhibits prostate cancer cell growth and metastasis via the caveolin-1/AKT/mTOR pathway. Molecular and Cellular Biochemistry, 406(1–2), 111–119. https://doi.org/10.1007/s11010-015-2429-8
Liu, H., Dong, Y. H., Gao, Y. T., Du, Z. P., Wang, Y. T., Cheng, P., et al. (2016). The fascinating effects of baicalein on cancer: A review. International Journal of Molecular Sciences, 17(10), ARTN 1681. https://doi.org/10.3390/ijms17101681.
Otsuyama, K. I., Ma, Z., Abroun, S., Amin, J., Shamsasenjan, K., Asaoku, H., et al. (2007). PPARbeta-mediated growth suppression of baicalein and dexamethasone in human myeloma cells. Leukemia, 21(1), 187–190. https://doi.org/10.1038/sj.leu.2404462
Carazo Fernandez, A., Smutny, T., Hyrsova, L., Berka, K., & Pavek, P. (2015). Chrysin, baicalein and galangin are indirect activators of the human constitutive androstane receptor (CAR). Toxicology Letters, 233(2), 68–77. https://doi.org/10.1016/j.toxlet.2015.01.013
Bonham, M., Posakony, J., Coleman, I., Montgomery, B., Simon, J., & Nelson, P. S. (2005). Characterization of chemical constituents in Scutellaria baicalensis with antiandrogenic and growth-inhibitory activities toward prostate carcinoma. Clinical Cancer Research, 11(10), 3905–3914. https://doi.org/10.1158/1078-0432.CCR-04-1974
Tsai, N. M., Chen, Y. L., Lee, C. C., Lin, P. C., Cheng, Y. L., Chang, W. L., et al. (2006). The natural compound n-butylidenephthalide derived from Angelica sinensis inhibits malignant brain tumor growth in vitro and in vivo. Journal of Neurochemistry, 99(4), 1251–1262. https://doi.org/10.1111/j.1471-4159.2006.04151.x
Tsai, N. M., Lin, S. Z., Lee, C. C., Chen, S. P., Su, H. C., Chang, W. L., et al. (2005). The antitumor effects of Angelica sinensis on malignant brain tumors in vitro and in vivo. Clinical Cancer Research, 11(9), 3475–3484. https://doi.org/10.1158/1078-0432.CCR-04-1827
Wei, C. W., Lin, C. C., Yu, Y. L., Lin, C. Y., Lin, P. C., Wu, M. T., et al. (2009). n-Butylidenephthalide induced apoptosis in the A549 human lung adenocarcinoma cell line by coupled down-regulation of AP-2alpha and telomerase activity. Acta Pharmacologica Sinica, 30(9), 1297–1306. https://doi.org/10.1038/aps.2009.124
Su, Y. J., Huang, S. Y., Ni, Y. H., Liao, K. F., & Chiu, S. C. (2018). Anti-tumor and radiosensitization effects of N-butylidenephthalide on human breast cancer cells. Molecules, 23(2), 240. https://doi.org/10.3390/molecules23020240
Chen, Y. L., Jian, M. H., Lin, C. C., Kang, J. C., Chen, S. P., Lin, P. C., et al. (2008). The induction of orphan nuclear receptor nur77 expression by n-butylenephthalide as pharmaceuticals on hepatocellular carcinoma cell therapy. Molecular Pharmacology, 74(4), 1046–1058. https://doi.org/10.1124/mol.107.044800
Lin, P. C., Chen, Y. L., Chiu, S. C., Yu, Y. L., Chen, S. P., Chien, M. H., et al. (2008). Orphan nuclear receptor, Nurr-77 was a possible target gene of butylidenephthalide chemotherapy on glioblastoma multiform brain tumor. Journal of Neurochemistry, 106(3), 1017–1026. https://doi.org/10.1111/j.1471-4159.2008.05432.x
Kannaiyan, R., Shanmugam, M. K., & Sethi, G. (2011). Molecular targets of celastrol derived from Thunder of God Vine: Potential role in the treatment of inflammatory disorders and cancer. Cancer Letters, 303(1), 9–20. https://doi.org/10.1016/j.canlet.2010.10.025
Sanna, V., Chamcheu, J. C., Pala, N., Mukhtar, H., Sechi, M., & Siddiqui, I. A. (2015). Nanoencapsulation of natural triterpenoid celastrol for prostate cancer treatment. International Journal of Nanomedicine, 10, 6835–6846. https://doi.org/10.2147/IJN.S93752
Lim, H. Y., Ong, P. S., Wang, L., Goel, A., Ding, L., Wong, A.L.-A., et al. (2021). Celastrol in cancer therapy: Recent developments, challenges and prospects. Cancer Letters, 521, 252–267.
Rajendran, P., Li, F., Shanmugam, M. K., Kannaiyan, R., Goh, J. N., Wong, K. F., et al. (2012). Celastrol suppresses growth and induces apoptosis of human hepatocellular carcinoma through the modulation of STAT3/JAK2 signaling cascade in vitro and in vivo. Cancer Prevention Research, 5(4), 631–643. https://doi.org/10.1158/1940-6207.Capr-11-0420
Li, X. J., Wang, H. M., Ding, J., Nie, S. Z., Wang, L., Zhang, L. L., et al. (2019). Celastrol strongly inhibits proliferation, migration and cancer stem cell properties through suppression of Pin1 in ovarian cancer cells. European Journal of Pharmacology, 842, 146–156. https://doi.org/10.1016/j.ejphar.2018.10.043
Yang, H. J., Chen, D., Cui, Q. Z. C., Yuan, X., & Dou, Q. P. (2006). Celastrol, a triterpene extracted from the Chinese “Thunder of God Vine”, is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice. Cancer Research, 66(9), 4758–4765. https://doi.org/10.1158/0008-5472.Can-05-4529
Hu, M. J., Luo, Q., Alitongbieke, G., Chong, S. Y., Xu, C. T., Xie, L., et al. (2017). Celastrol-induced Nur77 interaction with TRAF2 alleviates inflammation by promoting mitochondrial ubiquitination and autophagy. Molecular Cell, 66(1), 141-+, https://doi.org/10.1016/j.molcel.2017.03.008.
Chan, K., Chui, S., Wong, D., Ha, W., Chan, C., & Wong, R. (2004). Protective effects of Danshensu from the aqueous extract of Salvia miltiorrhiza (Danshen) against homocysteine-induced endothelial dysfunction. Life Sciences, 75(26), 3157–3171.
Chen, W., Lu, Y., Chen, G., & Huang, S. (2013). Molecular evidence of cryptotanshinone for treatment and prevention of human cancer. Anti-Cancer Agents in Medicinal Chemistry, 13(7), 979–987. https://doi.org/10.2174/18715206113139990115
Wu, C. Y., Hsieh, C. Y., Huang, K. E., Chang, C., & Kang, H. Y. (2012). Cryptotanshinone down-regulates androgen receptor signaling by modulating lysine-specific demethylase 1 function. International Journal of Cancer, 131(6), 1423–1434. https://doi.org/10.1002/ijc.27343
Xu, D., Lin, T. H., Li, S., Da, J., Wen, X. Q., Ding, J., et al. (2012). Cryptotanshinone suppresses androgen receptor-mediated growth in androgen dependent and castration resistant prostate cancer cells. Cancer Letters, 316(1), 11–22. https://doi.org/10.1016/j.canlet.2011.10.006
Moballegh Nasery, M., Abadi, B., Poormoghadam, D., Zarrabi, A., Keyhanvar, P., Khanbabaei, H., et al. (2020). Curcumin delivery mediated by bio-based nanoparticles: A review. Molecules, 25(3), 689.
Abadi, A. J., Mirzaei, S., Mahabady, M. K., Hashemi, F., Zabolian, A., Hashemi, F., et al. (2022). Curcumin and its derivatives in cancer therapy: Potentiating antitumor activity of cisplatin and reducing side effects. Phytotherapy Research, 36(1), 189–213.
Gupta, S. C., Sung, B., Kim, J. H., Prasad, S., Li, S., & Aggarwal, B. B. (2013). Multitargeting by turmeric, the golden spice: From kitchen to clinic. Molecular Nutrition & Food Research, 57(9), 1510–1528. https://doi.org/10.1002/mnfr.201100741
Bordoloi, D., Roy, N. K., Monisha, J., Padmavathi, G., & Kunnumakkara, A. B. (2016). Multi-targeted agents in cancer cell chemosensitization: What we learnt from curcumin thus far. Recent Patents on Anti-Cancer Drug Discovery, 11(1), 67–97. https://doi.org/10.2174/1574892810666151020101706
Giordano, A., & Tommonaro, G. (2019). Curcumin and cancer. Nutrients, 11(10), 2376.
Bhatia, M., Bhalerao, M., Cruz-Martins, N., & Kumar, D. (2021). Curcumin and cancer biology: Focusing regulatory effects in different signalling pathways. Phytotherapy Research, 35(9), 4913–4929. https://doi.org/10.1002/ptr.7121
Prakobwong, S., Gupta, S. C., Kim, J. H., Sung, B., Pinlaor, P., Hiraku, Y., et al. (2011). Curcumin suppresses proliferation and induces apoptosis in human biliary cancer cells through modulation of multiple cell signaling pathways. Carcinogenesis, 32(9), 1372–1380. https://doi.org/10.1093/carcin/bgr032
Peschel, D., Koerting, R., & Nass, N. (2007). Curcumin induces changes in expression of genes involved in cholesterol homeostasis. Journal of Nutritional Biochemistry, 18(2), 113–119. https://doi.org/10.1016/j.jnutbio.2006.03.007
Yang, F., Tang, X. W., Ding, L. L., Zhou, Y., Yang, Q. L., Gong, J. T., et al. (2016). Curcumin protects ANIT-induced cholestasis through signaling pathway of FXR-regulated bile acid and inflammation. Scientific Reports, 6, 33052. https://doi.org/10.1038/srep33052
Jiang, A., Wang, X., Shan, X., Li, Y., Wang, P., Jiang, P., et al. (2015). Curcumin reactivates silenced tumor suppressor gene RARβ by reducing DNA methylation. Phytotherapy Research, 29(8), 1237–1245.
Lee, Y. K., Lee, W. S., Hwang, J. T., Kwon, D. Y., Surh, Y. J., & Park, O. J. (2009). Curcumin exerts antidifferentiation effect through AMPKα-PPAR-γ in 3T3-L1 adipocytes and antiproliferatory effect through AMPKα-COX-2 in cancer cells. Journal of Agricultural and Food Chemistry, 57(1), 305–310.
Batie, S., Lee, J. H., Jama, R. A., Browder, D. O., Montano, L. A., Huynh, C. C., et al. (2013). Synthesis and biological evaluation of halogenated curcumin analogs as potential nuclear receptor selective agonists. Bioorganic & Medicinal Chemistry, 21(3), 693–702. https://doi.org/10.1016/j.bmc.2012.11.033
Bartik, L., Whitfield, G. K., Kaczmarska, M., Lowmiller, C. L., Moffet, E. W., Furmick, J. K., et al. (2010). Curcumin: A novel nutritionally derived ligand of the vitamin D receptor with implications for colon cancer chemoprevention. Journal of Nutritional Biochemistry, 21(12), 1153–1161. https://doi.org/10.1016/j.jnutbio.2009.09.012
Chen, A. P., & Xu, J. Y. (2005). Activation of PPAR gamma by curcumin inhibits Moser cell growth and mediates suppression of gene expression of cyclin D1 and EGFR. American Journal of Physiology-Gastrointestinal and Liver Physiology, 288(3), G447-G456, https://doi.org/10.1152/ajpgi.00209.2004.
Thulasiraman, P., Garriga, G., Danthuluri, V., McAndrews, D. J., & Mohiuddin, I. Q. (2017). Activation of the CRABPII/RAR pathway by curcumin induces retinoic acid mediated apoptosis in retinoic acid resistant breast cancer cells. Oncology Reports, 37(4), 2007–2015. https://doi.org/10.3892/or.2017.5495
Thulasiraman, P., McAndrews, D. J., & Mohiudddin, I. Q. (2014). Curcumin restores sensitivity to retinoic acid in triple negative breast cancer cells. Bmc Cancer, 14, 724. https://doi.org/10.1186/1471-2407-14-724
Altenburg, J. D., Bieberich, A. A., Terry, C., Harvey, K. A., VanHorn, J. F., Xu, Z., et al. (2011). A synergistic antiproliferation effect of curcumin and docosahexaenoic acid in SK-BR-3 breast cancer cells: Unique signaling not explained by the effects of either compound alone. BMC Cancer, 11(1), 1–16.
Mullen, W., Yokota, T., Lean, M. E., & Crozier, A. (2003). Analysis of ellagitannins and conjugates of ellagic acid and quercetin in raspberry fruits by LC-MSn. Phytochemistry, 64(2), 617–624. https://doi.org/10.1016/s0031-9422(03)00281-4
Berni, A., Grossi, M. R., Pepe, G., Filippi, S., Muthukumar, S., Papeschi, C., et al. (2012). Protective effect of ellagic acid (EA) on micronucleus formation induced by N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) in mammalian cells, in in vitro assays and in vivo. Mutation Research, 746(1), 60–65. https://doi.org/10.1016/j.mrgentox.2012.03.007
Kumar, K. N., Raja, S. B., Vidhya, N., & Devaraj, S. N. (2012). Ellagic acid modulates antioxidant status, ornithine decarboxylase expression, and aberrant crypt foci progression in 1,2-dimethylhydrazine-instigated colon preneoplastic lesions in rats. Journal of Agriculture and Food Chemistry, 60(14), 3665–3672. https://doi.org/10.1021/jf204128z
Khanduja, K. L., Gandhi, R. K., Pathania, V., & Syal, N. (1999). Prevention of N-nitrosodiethylamine-induced lung tumorigenesis by ellagic acid and quercetin in mice. Food and Chemical Toxicology, 37(4), 313–318. https://doi.org/10.1016/s0278-6915(99)00021-6
Anitha, P., Priyadarsini, R. V., Kavitha, K., Thiyagarajan, P., & Nagini, S. (2013). Ellagic acid coordinately attenuates Wnt/beta-catenin and NF-kappaB signaling pathways to induce intrinsic apoptosis in an animal model of oral oncogenesis. European Journal of Nutrition, 52(1), 75–84. https://doi.org/10.1007/s00394-011-0288-y
Munagala, R., Aqil, F., Vadhanam, M. V., & Gupta, R. C. (2013). MicroRNA ‘signature’ during estrogen-mediated mammary carcinogenesis and its reversal by ellagic acid intervention. Cancer Letters, 339(2), 175–184. https://doi.org/10.1016/j.canlet.2013.06.012
Hong, M. Y., Seeram, N. P., & Heber, D. (2008). Pomegranate polyphenols down-regulate expression of androgen-synthesizing genes in human prostate cancer cells overexpressing the androgen receptor. Journal of Nutritional Biochemistry, 19(12), 848–855. https://doi.org/10.1016/j.jnutbio.2007.11.006
Kim, S. W., Kim, S. M., Bae, H., Nam, D., Lee, J. H., Lee, S. G., et al. (2013). Embelin inhibits growth and induces apoptosis through the suppression of Akt/mTOR/S6K1 signaling cascades. The Prostate, 73(3), 296–305.
Ko, J. H., Lee, S. G., Yang, W. M., Um, J. Y., Sethi, G., Mishra, S., et al. (2018). The application of embelin for cancer prevention and therapy. Molecules, 23(3), ARTN 621. https://doi.org/10.3390/molecules23030621.
Manu, K. A., Shanmugam, M. K., Ong, T. H., Subramaniam, A., Siveen, K. S., Perumal, E., et al. (2013). Emodin suppresses migration and invasion through the modulation of CXCR4 expression in an orthotopic model of human hepatocellular carcinoma. PLoS One, 8(3), e57015.
Subramaniam, A., Loo, S. Y., Rajendran, P., Manu, K. A., Perumal, E., Li, F., et al. (2013). An anthraquinone derivative, emodin sensitizes hepatocellular carcinoma cells to TRAIL induced apoptosis through the induction of death receptors and downregulation of cell survival proteins. Apoptosis, 18(10), 1175–1187.
Cha, T. L., Qiu, L., Chen, C. T., Wen, Y., & Hung, M. C. (2005). Emodin down-regulates androgen receptor and inhibits prostate cancer cell growth. Cancer Research, 65(6), 2287–2295. https://doi.org/10.1158/0008-5472.CAN-04-3250
Hsu, C. M., Hsu, Y. A., Tsai, Y., Shieh, F. K., Huang, S. H., Wan, L., et al. (2010). Emodin inhibits the growth of hepatoma cells: Finding the common anti-cancer pathway using Huh7, Hep3B, and HepG2 cells. Biochemical and Biophysical Research Communications, 392(4), 473–478. https://doi.org/10.1016/j.bbrc.2009.10.153
Tuli, H. S., Tuorkey, M. J., Thakral, F., Sak, K., Kumar, M., Sharma, A. K., et al. (2019). Molecular mechanisms of action of genistein in cancer: Recent advances. Frontiers in Pharmacology, 10, 1336. https://doi.org/10.3389/fphar.2019.01336
Bektic, J., Berger, A. P., Pfeil, K., Dobler, G., Bartsch, G., & Klocker, H. (2004). Androgen receptor regulation by physiological concentrations of the isoflavonoid genistein in androgen-dependent LNCaP cells is mediated by estrogen receptor β. European Urology, 45(2), 245–251.
Mahmoud, A. M., Al-Alem, U., Ali, M. M., & Bosland, M. C. (2015). Genistein increases estrogen receptor beta expression in prostate cancer via reducing its promoter methylation. Journal of Steroid Biochemistry and Molecular Biology, 152, 62–75. https://doi.org/10.1016/j.jsbmb.2015.04.018
Basak, S., Pookot, D., Noonan, E. J., & Dahiya, R. (2008). Genistein down-regulates androgen receptor by modulating HDAC6-Hsp90 chaperone function. Molecular Cancer Therapeutics, 7(10), 3195–3202. https://doi.org/10.1158/1535-7163.MCT-08-0617
Oh, H. Y., Leem, J., Yoon, S. J., Yoon, S., & Hong, S. J. (2010). Lipid raft cholesterol and genistein inhibit the cell viability of prostate cancer cells via the partial contribution of EGFR-Akt/p70S6k pathway and down-regulation of androgen receptor. Biochemical and Biophysical Research Communications, 393(2), 319–324. https://doi.org/10.1016/j.bbrc.2010.01.133
Gao, S., Liu, G. Z., & Wang, Z. (2004). Modulation of androgen receptor-dependent transcription by resveratrol and genistein in prostate cancer cells. Prostate, 59(2), 214–225. https://doi.org/10.1002/pros.10375
Zhang, T., Wang, F., Xu, H. X., Yi, L., Qin, Y., Chang, H., et al. (2013). Activation of nuclear factor erythroid 2-related factor 2 and PPARgamma plays a role in the genistein-mediated attenuation of oxidative stress-induced endothelial cell injury. British Journal of Nutrition, 109(2), 223–235. https://doi.org/10.1017/S0007114512001110
Huang, S. L., Chang, T. C., Chao, C. C. K., & Sun, N. K. (2020). Role of the TLR4-androgen receptor axis and genistein in taxol-resistant ovarian cancer cells. Biochemical Pharmacology, 177, 113965. https://doi.org/10.1016/j.bcp.2020.113965
Shen, P., Liu, M. H., Ng, T. Y., Chan, Y. H., & Yong, E. L. (2006). Differential effects of isoflavones, from Astragalus membranaceus and Pueraria thomsonii, on the activation of PPARalpha, PPARgamma, and adipocyte differentiation in vitro. Journal of Nutrition, 136(4), 899–905. https://doi.org/10.1093/jn/136.4.899
Ahn, K. S., Sethi, G., Sung, B., Goel, A., Ralhan, R., & Aggarwal, B. B. (2008). Guggulsterone, a farnesoid X receptor antagonist, inhibits constitutive and inducible STAT3 activation through induction of a protein tyrosine phosphatase SHP-1 (Publication with Expression of Concern. See vol. 78, pg. 5184, 2018). Cancer Research, 68(11), 4406–4415, https://doi.org/10.1158/0008-5472.Can-07-6696.
Shishodia, S., Harikumar, K. B., Dass, S., Ramawat, K. G., & Aggarwal, B. B. (2008). The guggul for chronic diseases: Ancient medicine, modern targets. Anticancer Research, 28(6a), 3647–3664.
Girisa, S., Parama, D., Harsha, C., Banik, K., & Kunnumakkara, A. B. (2020). Potential of guggulsterone, a farnesoid X receptor antagonist, in the prevention and treatment of cancer. Exploration of Targeted Anti-tumor Theraphy, 1(5), 313–342, https://doi.org/10.37349/etat.2020.00019.
Bhat, A. A., Prabhu, K. S., Kuttikrishnan, S., Krishnankutty, R., Babu, J., Mohammad, R. M., et al. (2017). Potential therapeutic targets of guggulsterone in cancer. Nutrition & Metabolism, 14, 23. https://doi.org/10.1186/s12986-017-0180-8
Guan, B. X., Li, H., Yang, Z. D., Hoque, A., & Xu, X. C. (2013). Inhibition of farnesoid X receptor controls esophageal cancer cell growth in vitro and in nude mouse xenografts. Cancer, 119(7), 1321–1329. https://doi.org/10.1002/cncr.27910
Chen, Y., Wang, H. H., Chang, H. H., Huang, Y. H., Wang, J. R., Changchien, C. Y., et al. (2021). Guggulsterone induces apoptosis and inhibits lysosomal-dependent migration in human bladder cancer cells. Phytomedicine, 87, 153587. https://doi.org/10.1016/j.phymed.2021.153587
Yu, J.-H., Zheng, J.-B., Qi, J., Yang, K., Wu, Y.-H., Wang, K., et al. (2019). Bile acids promote gastric intestinal metaplasia by upregulating CDX2 and MUC2 expression via the FXR/NF-κB signalling pathway. International Journal of Oncology, 54(3), 879–892.
Urizar, N. L., Liverman, A. B., Dodds, D. T., Silva, F. V., Ordentlich, P., Yan, Y. Z., et al. (2002). A natural product that lowers cholesterol as an antagonist ligand for FXR. Science, 296(5573), 1703–1706. https://doi.org/10.1126/science.1072891
Lee, J., Lee, K., Lee, J., Lee, K., Jang, K., Heo, J., et al. (2011). Farnesoid X receptor, overexpressed in pancreatic cancer with lymph node metastasis promotes cell migration and invasion. British Journal of Cancer, 104(6), 1027–1037.
Kong, J. N., He, Q., Wang, G. H., Dasgupta, S., Dinkins, M. B., Zhu, G., et al. (2015). Guggulsterone and bexarotene induce secretion of exosome-associated breast cancer resistance protein and reduce doxorubicin resistance in MDA-MB-231 cells. International Journal of Cancer, 137(7), 1610–1620. https://doi.org/10.1002/ijc.29542
Tian, H., Gui, Y. N., Wei, Y. H., Shang, B., Sun, J., Ma, S., et al. (2021). Z-guggulsterone induces PD-L1 upregulation partly mediated by FXR, Akt and Erk1/2 signaling pathways in non-small cell lung cancer. International Immunopharmacology, 93, 107395. https://doi.org/10.1016/j.intimp.2021.107395
Kao, T. H., Huang, S. C., Inbaraj, B. S., & Chen, B. H. (2008). Determination of flavonoids and saponins in Gynostemma pentaphyllum (Thunb.) Makino by liquid chromatography-mass spectrometry. Analytica Chimica Acta, 626(2), 200–211, https://doi.org/10.1016/j.aca.2008.07.049.
Wang, J., & Zhao, J. (1993). The effect of preventing recurrence of cancer metastasis on jiaogulan soup in clinical study. Zhejiang Zhong Yi Za Zhii, 28(20), 529–530.
Piao, X. L., Wu, Q., Yang, J., Park, S. Y., Chen, D. J., & Liu, H. M. (2013). Dammarane-type saponins from heat-processed Gynostemma pentaphyllum show fortified activity against A549 cells. Archives of Pharmacal Research, 36(7), 874–879. https://doi.org/10.1007/s12272-013-0086-6
Piao, X. L., Xing, S. F., Lou, C. X., & Chen, D. J. (2014). Novel dammarane saponins from Gynostemma pentaphyllum and their cytotoxic activities against HepG2 cells. Bioorganic & Medicinal Chemistry Letters, 24(20), 4831–4833. https://doi.org/10.1016/j.bmcl.2014.08.059
Chen, D. J., Liu, H. M., Xing, S. F., & Piao, X. L. (2014). Cytotoxic activity of gypenosides and gynogenin against non-small cell lung carcinoma A549 cells. Bioorganic & Medicinal Chemistry Letters, 24(1), 186–191. https://doi.org/10.1016/j.bmcl.2013.11.043
Xing, S. F., Liu, L. H., Zu, M. L., Ding, X. F., Cui, W. Y., Chang, T., et al. (2018). The inhibitory effect of gypenoside stereoisomers, gypenoside L and gypenoside LI, isolated from Gynostemma pentaphyllum on the growth of human lung cancer A549 cells. Journal of Ethnopharmacology, 219, 161–172. https://doi.org/10.1016/j.jep.2018.03.012
Huang, T. H., Tran, V. H., Roufogalis, B. D., & Li, Y. (2007). Gypenoside XLIX, a naturally occurring gynosaponin, PPAR-alpha dependently inhibits LPS-induced tissue factor expression and activity in human THP-1 monocytic cells. Toxicology and Applied Pharmacology, 218(1), 30–36. https://doi.org/10.1016/j.taap.2006.10.013
Aggarwal, V., Tuli, H. S., Thakral, F., Singhal, P., Aggarwal, D., Srivastava, S., et al. (2020). Molecular mechanisms of action of hesperidin in cancer: Recent trends and advancements. Experimental Biology and Medicine (Maywood, N.J.), 245(5), 486–497. https://doi.org/10.1177/1535370220903671
Ahmadi, A., & Shadboorestan, A. (2016). Oxidative stress and cancer; the role of hesperidin, a citrus natural bioflavonoid, as a cancer chemoprotective agent. Nutrition and Cancer, 68(1), 29–39.
Saiprasad, G., Chitra, P., Manikandan, R., & Sudhandiran, G. (2014). Hesperidin induces apoptosis and triggers autophagic markers through inhibition of Aurora-A mediated phosphoinositide-3-kinase/Akt/mammalian target of rapamycin and glycogen synthase kinase-3 beta signalling cascades in experimental colon carcinogenesis. European Journal of Cancer, 50(14), 2489–2507. https://doi.org/10.1016/j.ejca.2014.06.013
Wang, Y. X., Yu, H., Zhang, J., Gao, J., Ge, X., & Lou, G. (2015). Hesperidin inhibits HeLa cell proliferation through apoptosis mediated by endoplasmic reticulum stress pathways and cell cycle arrest. Bmc Cancer, 15, 682. https://doi.org/10.1186/s12885-015-1706-y
Khamis, A. A. A., Ali, E. M. M., Abd El-Moneim, M. A., Abd-Alhaseeb, M. M., Abu El-Magd, M., & Salim, E. I. (2018). Hesperidin, piperine and bee venom synergistically potentiate the anticancer effect of tamoxifen against breast cancer cells. Biomedicine & Pharmacotherapy, 105, 1335–1343. https://doi.org/10.1016/j.biopha.2018.06.105
Hsu, P. H., Chen, W. H., Chen, J. L., Hsieh, S. C., Lin, S. C., Mai, R. T., et al. (2021). Hesperidin and chlorogenic acid synergistically inhibit the growth of breast cancer cells via estrogen receptor/mitochondrial pathway. Life-Basel, 11(9), ARTN 950. https://doi.org/10.3390/life11090950.
Banik, K., Ranaware, A. M., Deshpande, V., Nalawade, S. P., Padmavathi, G., Bordoloi, D., et al. (2019). Honokiol for cancer therapeutics: A traditional medicine that can modulate multiple oncogenic targets. Pharmacological Research, 144, 192–209.
Arora, S., Singh, S., Piazza, G. A., Contreras, C. M., Panyam, J., & Singh, A. P. (2012). Honokiol: A novel natural agent for cancer prevention and therapy. Current Molecular Medicine, 12(10), 1244–1252. https://doi.org/10.2174/156652412803833508
Ong, C. P., Lee, W. L., Tang, Y. Q., & Yap, W. H. (2020). Honokiol: A review of its anticancer potential and mechanisms. Cancers, 12(1), ARTN 48. https://doi.org/10.3390/cancers12010048.
Jung, C. G., Horike, H., Cha, B. Y., Uhm, K. O., Yamauchi, R., Yamaguchi, T., et al. (2010). Honokiol increases ABCA1 expression level by activating retinoid X receptor beta. Biological & Pharmaceutical Bulletin, 33(7), 1105–1111. https://doi.org/10.1248/bpb.33.1105
Lim, S. L., Park, S. Y., Kang, S., Park, D., Kim, S. H., Um, J. Y., et al. (2015). Morusin induces cell death through inactivating STAT3 signaling in prostate cancer cells. American Journal of Cancer Research, 5(1), 289-U482.
Lin, W. L., Lai, D. Y., Lee, Y. J., Chen, N. F., & Tseng, T. H. (2015). Antitumor progression potential of morusin suppressing STAT3 and NFkappaB in human hepatoma SK-Hep1 cells. Toxicology Letters, 232(2), 490–498. https://doi.org/10.1016/j.toxlet.2014.11.031
Dat, N. T., Binh, P. T. X., Van Minh, C., Huong, H. T., & Lee, J. J. (2010). Cytotoxic prenylated flavonoids from Morus alba. Fitoterapia, 81(8), 1224–1227.
Wan, L. Z., Ma, B., & Zhang, Y. Q. (2014). Preparation of morusin from Ramulus mori and its effects on mice with transplanted H22 hepatocarcinoma. BioFactors, 40(6), 636–645. https://doi.org/10.1002/biof.1191
Lee, J.-C., Won, S.-J., Chao, C.-L., Wu, F.-L., Liu, H.-S., Ling, P., et al. (2008). Morusin induces apoptosis and suppresses NF-κB activity in human colorectal cancer HT-29 cells. Biochemical and Biophysical Research Communications, 372(1), 236–242.
Li, H., Wang, Q., Dong, L., Liu, C., Sun, Z., Gao, L., et al. (2015). Morusin suppresses breast cancer cell growth in vitro and in vivo through C/EBPβ and PPARγ mediated lipoapoptosis. Journal of Experimental & Clinical Cancer Research, 34(1), 1–12.
Baek, S. H., Ko, J.-H., Lee, H., Jung, J., Kong, M., Lee, J.-W., et al. (2016). Resveratrol inhibits STAT3 signaling pathway through the induction of SOCS-1: Role in apoptosis induction and radiosensitization in head and neck tumor cells. Phytomedicine, 23(5), 566–577.
Ren, B., Kwah, M. X., Liu, C., Ma, Z., Shanmugam, M. K., Ding, L., et al. (2021). Resveratrol for cancer therapy: Challenges and future perspectives. Cancer Letters, 515, 63–72. https://doi.org/10.1016/j.canlet.2021.05.001
Nonomura, S., Kanagawa, H., & Makimoto, A. (1963). Chemical Constituents of Polygonaceous Plants. I. Studies on the Components of Ko-J O-Kon. (Polygonum Cuspidatum Sieb. Et Zucc.). Yakugaku Zasshi, 83, 988–990.
Diaz, J., Wuertz, B., Galbraith, A., & Ondrey, F. G. (2016). Effects of chalcones, nicotinamide, and resveratrol on PPAR gamma activation in oral cancer cells. Cancer Research, 76, 2611. https://doi.org/10.1158/1538-7445.Am2016-2611
Ulrich, S., Loitsch, S. M., Rau, O., von Knethen, A., Brune, B., Schubert-Zsilavecz, M., et al. (2006). Peroxisome proliferator-activated receptor gamma as a molecular target of resveratrol-induced modulation of polyamine metabolism. Cancer Research, 66(14), 7348–7354. https://doi.org/10.1158/0008-5472.Can-05-2777
Li, Y. T., Tian, X. T., Wu, M. L., Zheng, X., Kong, Q. Y., Cheng, X. X., et al. (2018). Resveratrol suppresses the growth and enhances retinoic acid sensitivity of anaplastic thyroid cancer cells. International Journal of Molecular Sciences, 19(4), ARTN 1030. https://doi.org/10.3390/ijms19041030.
Vanden Berghe, W., Sabbe, L., Kaileh, M., Haegeman, G., & Heyninck, K. (2012). Molecular insight in the multifunctional activities of withaferin A. Biochemical Pharmacology, 84(10), 1282–1291. https://doi.org/10.1016/j.bcp.2012.08.027
Bargagna-Mohan, P., Hamza, A., Kim, Y. E., Ho, K. A., Y., Mor-Vaknin, N., Wendschlag, N., et al. (2007). The tumor inhibitor and antiangiogenic agent withaferin A targets the intermediate filament protein vimentin. Chemistry & Biology, 14(6), 623–634. https://doi.org/10.1016/j.chembiol.2007.04.010
Shiragannavar, V. D., Gowda, N. G. S., Kumar, D. P., Mirshahi, F., & Santhekadur, P. K. (2021). Withaferin A acts as a novel regulator of liver X receptor-α in HCC. Frontiers in Oncology, 3124.
Lim, Y. P., Cheng, C. H., Chen, W. C., Chang, S. Y., Hung, D. Z., Chen, J. J., et al. (2015). Allyl isothiocyanate (AITC) inhibits pregnane X receptor (PXR) and constitutive androstane receptor (CAR) activation and protects against acetaminophen- and amiodarone-induced cytotoxicity. Archives of Toxicology, 89(1), 57–72. https://doi.org/10.1007/s00204-014-1230-x
Oh, H., Park, S.-H., Kang, M.-K., Kim, Y.-H., Lee, E.-J., Kim, D. Y., et al. (2020). Asaronic acid inhibited glucose-triggered M2-phenotype shift through disrupting the formation of coordinated signaling of IL-4Rα-Tyk2-STAT6 and GLUT1-Akt-mTOR-AMPK. Nutrients, 12(7), 2006.
Papaioannou, M., Schleich, S., Prade, I., Degen, S., Roell, D., Schubert, U., et al. (2009). The natural compound atraric acid is an antagonist of the human androgen receptor inhibiting cellular invasiveness and prostate cancer cell growth. Journal of Cellular and Molecular Medicine, 13(8b), 2210–2223. https://doi.org/10.1111/j.1582-4934.2008.00426.x
Schleich, S., Papaioannou, M., Baniahmad, A., & Matusch, R. (2006). Extracts from Pygeum africanum and other ethnobotanical species with antiandrogenic activity. Planta Medica, 72(9), 807–813. https://doi.org/10.1055/s-2006-946638
Papaioannou, M., Schleich, S., Roell, D., Schubert, U., Tanner, T., Claessens, F., et al. (2010). NBBS isolated from Pygeum africanum bark exhibits androgen antagonistic activity, inhibits AR nuclear translocation and prostate cancer cell growth. Investigational New Drugs, 28(6), 729–743. https://doi.org/10.1007/s10637-009-9304-y
Fiaschetti, G., Grotzer, M. A., Shalaby, T., Castelletti, D., & Arcaro, A. (2011). Quassinoids: From traditional drugs to new cancer therapeutics. Current Medicinal Chemistry, 18(3), 316–328. https://doi.org/10.2174/092986711794839205
Moon, S. J., Jeong, B. C., Kim, H. J., Lim, J. E., Kim, H. J., Kwon, G. Y., et al. (2021). Bruceantin targets HSP90 to overcome resistance to hormone therapy in castration-resistant prostate cancer. Theranostics, 11(2), 958–973. https://doi.org/10.7150/thno.51478
Xu, D., Lin, T. H., Yeh, C. R., Cheng, M. A., Chen, L. M., Chang, C., et al. (2014). The wedelolactone derivative inhibits estrogen receptor-mediated breast, endometrial, and ovarian cancer cells growth. BioMed Research International, 2014, 713263. https://doi.org/10.1155/2014/713263
Akihisa, T., Higo, N., Tokuda, H., Ukiya, M., Akazawa, H., Tochigi, Y., et al. (2007). Cucurbitane-type triterpenoids from the fruits of Momordica charantia and their cancer chemopreventive effects. Journal of Natural Products, 70(8), 1233–1239. https://doi.org/10.1021/np068075p
Weng, J.-R., Bai, L.-Y., Chiu, C.-F., Hu, J.-L., Chiu, S.-J., & Wu, C.-Y. (2013). Cucurbitane triterpenoid from Momordica charantia induces apoptosis and autophagy in breast cancer cells, in part, through peroxisome proliferator-activated receptor γ activation. Evidence-Based Complementary and Alternative Medicine, 2013, 93675. https://doi.org/10.1155/2013/935675
Somjen, D., Grafi-Cohen, M., Weisinger, G., Izkhakov, E., Sharon, O., Kraiem, Z., et al. (2012). Growth inhibition of human thyroid carcinoma and goiter cells in vitro by the isoflavone derivative 7-(O)-carboxymethyl daidzein conjugated to Nt-boc-hexylenediamine. Thyroid, 22(8), 809–813.
Ichikawa, H., Nair, M. S., Takada, Y., Sheeja, D. A., Kumar, M. S., Oommen, O. V., et al. (2006). Isodeoxyelephantopin, a novel sesquiterpene lactone, potentiates apoptosis, inhibits invasion, and abolishes osteoclastogenesis through suppression of nuclear factor-κB (NF-κB) activation and NF-κB-regulated gene expression. Clinical Cancer Research, 12(19), 5910–5918.
Wolo, M. T., Cowherd, C. M., & Lee, K. H. (1975). Antitumor agents XV: Deoxyelephantopin, an antitumor principle from Elephantopus carolinianus Willd. Journal of Pharmaceutical Sciences, 64(9), 1572–1573.
Zou, G., Gao, Z., Wang, J., Zhang, Y., Ding, H., Huang, J., et al. (2008). Deoxyelephantopin inhibits cancer cell proliferation and functions as a selective partial agonist against PPARγ. Biochemical Pharmacology, 75(6), 1381–1392.
Jung, Y. S., Lee, H. S., Cho, H. R., Kim, K. J., Kim, J. H., Safe, S., et al. (2019). Dual targeting of Nur77 and AMPKalpha by isoalantolactone inhibits adipogenesis in vitro and decreases body fat mass in vivo. International Journal of Obesity, 43(5), 952–962. https://doi.org/10.1038/s41366-018-0276-x
Cao, Y., Chu, Q., & Ye, J. (2004). Chromatographic and electrophoretic methods for pharmaceutically active compounds in Rhododendron dauricum. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 812(1–2), 231–240. https://doi.org/10.1016/j.jchromb.2004.06.048
Chae, J., Kim, J. S., Choi, S. T., Lee, S. G., Ojulari, O. V., Kang, Y. J., et al. (2021). Farrerol induces cancer cell death via ERK activation in SKOV3 cells and attenuates TNF-alpha-mediated lipolysis. International Journal of Molecular Sciences, 22(17), 9400. https://doi.org/10.3390/ijms22179400
Neviani, P., Santhanam, R., Trotta, R., Notari, M., Blaser, B. W., Liu, S. J., et al. (2005). The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein. Cancer Cell, 8(5), 355–368. https://doi.org/10.1016/j.ccr.2005.10.015
Mayati, A., Moreau, A., Le Vee, M., Bruyere, A., Jouan, E., Denizot, C., et al. (2018). Functional polarization of human hepatoma HepaRG cells in response to forskolin. Scientific Reports, 8(1), 16115. https://doi.org/10.1038/s41598-018-34421-8
Roullet, J. B., Luft, U. C., Xue, H., Chapman, J., Bychkov, R., Roullet, C. M., et al. (1997). Farnesol inhibits L-type Ca2+ channels in vascular smooth muscle cells. Journal of Biological Chemistry, 272(51), 32240–32246. https://doi.org/10.1074/jbc.272.51.32240
Mo, H., & Elson, C. E. (1999). Apoptosis and cell-cycle arrest in human and murine tumor cells are initiated by isoprenoids. Journal of Nutrition, 129(4), 804–813. https://doi.org/10.1093/jn/129.4.804
He, L., Mo, H., Hadisusilo, S., Qureshi, A. A., & Elson, C. E. (1997). Isoprenoids suppress the growth of murine B16 melanomas in vitro and in vivo. Journal of Nutrition, 127(5), 668–674. https://doi.org/10.1093/jn/127.5.668
Takahashi, N., Kawada, T., Goto, T., Yamamoto, T., Taimatsu, A., Matsui, N., et al. (2002). Dual action of isoprenols from herbal medicines on both PPARγ and PPARα in 3T3-L1 adipocytes and HepG2 hepatocytes. FEBS Letters, 514(2–3), 315–322.
Kim, Y. S., & Milner, J. A. (2005). Targets for indole-3-carbinol in cancer prevention. Journal of Nutritional Biochemistry, 16(2), 65–73. https://doi.org/10.1016/j.jnutbio.2004.10.007
Marconett, C. N., Sundar, S. N., Poindexter, K. M., Stueve, T. R., Bjeldanes, L. F., & Firestone, G. L. (2010). Indole-3-carbinol triggers aryl hydrocarbon receptor-dependent estrogen receptor (ER)alpha protein degradation in breast cancer cells disrupting an ERalpha-GATA3 transcriptional cross-regulatory loop. Molecular Biology of the Cell, 21(7), 1166–1177. https://doi.org/10.1091/mbc.E09-08-0689
Hsu, J. C., Zhang, J., Dev, A., Wing, A., Bjeldanes, L. F., & Firestone, G. L. (2005). Indole-3-carbinol inhibition of androgen receptor expression and downregulation of androgen responsiveness in human prostate cancer cells. Carcinogenesis, 26(11), 1896–1904.
Patel, A. R., Spencer, S. D., Chougule, M. B., Safe, S., & Singh, M. (2012). Pharmacokinetic evaluation and in vitro-in vivo correlation (IVIVC) of novel methylene-substituted 3,3’ diindolylmethane (DIM). European Journal of Pharmaceutical Sciences, 46(1–2), 8–16. https://doi.org/10.1016/j.ejps.2012.01.012
Boakye, C. H. A., Doddapaneni, R., Shah, P. P., Patel, A. R., Godugu, C., Safe, S., et al. (2013). Chemoprevention of skin cancer with 1,1-bis (3'-indolyl)-1-(aromatic) methane analog through induction of the orphan nuclear receptor, NR4A2 (Nurr1). Plos One, 8(8), ARTN e69519. https://doi.org/10.1371/journal.pone.0069519.
Yang, L., Zahid, M., Liao, Y., Rogan, E. G., Cavalieri, E. L., Davidson, N. E., et al. (2013). Reduced formation of depurinating estrogen-DNA adducts by sulforaphane or KEAP1 disruption in human mammary epithelial MCF-10A cells. Carcinogenesis, 34(11), 2587–2592. https://doi.org/10.1093/carcin/bgt246
Palliyaguru, D. L., Yang, L., Chartoumpekis, D. V., Wendell, S. G., Fazzari, M., Skoko, J. J., et al. (2020). Sulforaphane diminishes the formation of mammary tumors in rats exposed to 17beta-estradiol. Nutrients, 12(8), 2282. https://doi.org/10.3390/nu12082282
Hossain, S., Liu, Z. H., & Wood, R. J. (2020). Histone deacetylase activity and vitamin D-dependent gene expressions in relation to sulforaphane in human breast cancer cells. Journal of Food Biochemistry, 44(2), ARTN e13114. https://doi.org/10.1111/jfbc.13114.
Hossain, S., Liu, Z. H., & Wood, R. J. (2021). Association between histone deacetylase activity and vitamin D-dependent gene expressions in relation to sulforaphane in human colorectal cancer cells. Journal of the Science of Food and Agriculture, 101(5), 1833–1843. https://doi.org/10.1002/jsfa.10797
Zhou, C. C., Poulton, E. J., Grun, F., Bammler, T. K., Blumberg, B., Thummel, K. E., et al. (2007). The dietary isothiocyanate sulforaphane is an antagonist of the human steroid and xenobiotic nuclear receptor. Molecular Pharmacology, 71(1), 220–229. https://doi.org/10.1124/mol.106.029264
Liu, Y. X., Xie, S. R., Wang, Y., Luo, K., Wang, Y., & Cai, Y. Q. (2012). Liquiritigenin inhibits tumor growth and vascularization in a mouse model of hela cells. Molecules, 17(6), 7206–7216. https://doi.org/10.3390/molecules17067206
Mersereau, J. E., Levy, N., Staub, R. E., Baggett, S., Zogric, T., Chow, S., et al. (2008). Liquiritigenin is a plant-derived highly selective estrogen receptor beta agonist. Molecular and Cellular Endocrinology, 283(1–2), 49–57. https://doi.org/10.1016/j.mce.2007.11.020
Ranaware, A. M., Banik, K., Deshpande, V., Padmavathi, G., Roy, N. K., Sethi, G., et al. (2018). Magnolol: A neolignan from the magnolia family for the prevention and treatment of cancer. International Journal of Molecular Sciences, 19(8), https://doi.org/10.3390/ijms19082362.
Peng, C. Y., Yu, C. C., Huang, C. C., Liao, Y. W., Hsieh, P. L., Chu, P. M., et al. (2022). Magnolol inhibits cancer stemness and IL-6/Stat3 signaling in oral carcinomas. Journal of the Formosan Medical Association, 121(1 Pt 1), 51–57. https://doi.org/10.1016/j.jfma.2021.01.009
Tian, Y., Feng, H., Han, L., Wu, L., Lv, H., Shen, B., et al. (2018). Magnolol alleviates inflammatory responses and lipid accumulation by AMP-activated protein kinase-dependent peroxisome proliferator-activated receptor alpha activation. Frontiers in Immunology, 9, 147. https://doi.org/10.3389/fimmu.2018.00147
Lu, Y., Sun, Y., Zhu, J., Yu, L., Jiang, X., Zhang, J., et al. (2018). Oridonin exerts anticancer effect on osteosarcoma by activating PPAR-gamma and inhibiting Nrf2 pathway. Cell Death & Disease, 9(1), 15. https://doi.org/10.1038/s41419-017-0031-6
Rontani, J. F., & Volkman, J. K. (2003). Phytol degradation products as biogeochemical tracers in aquatic environments.Organic Geochemistry, 34(1), 1–35, Pii S0146–6380(02)00185–7. https://doi.org/10.1016/S0146-6380(02)00185-7.
Goto, T., Takahashi, N., Kato, S., Egawa, K., Ebisu, S., Moriyama, T., et al. (2005). Phytol directly activates peroxisome proliferator-activated receptor alpha (PPARalpha) and regulates gene expression involved in lipid metabolism in PPARalpha-expressing HepG2 hepatocytes. Biochemical and Biophysical Research Communications, 337(2), 440–445. https://doi.org/10.1016/j.bbrc.2005.09.077
Yang, A. O. S. H., Tongson, J., Kim, K. H., & Park, Y. (2020). Piceatannol attenuates fat accumulation and oxidative stress in steatosis-induced HepG2 cells. Current Research in Food Science, 3, 92–99. https://doi.org/10.1016/j.crfs.2020.03.008
He, T., Wu, K., Lv, Y., Gong, X., Chen, G. G., & Liang, N. (2009). Effect of 5F from Pteris semipinnata on expression of Nr1d1 in HO-8910PM cell line. Zhongguo Zhong Yao Za Zhi, 34(10), 1268–1271.
Tan, B. S., Kang, O., Mai, C. W., Tiong, K. H., Khoo, A. S. B., Pichika, M. R., et al. (2013). 6-Shogaol inhibits breast and colon cancer cell proliferation through activation of peroxisomal proliferator activated receptor gamma (PPAR gamma). Cancer Letters, 336(1), 127–139. https://doi.org/10.1016/j.canlet.2013.04.014
Shanmugam, M. K., Ahn, K. S., Hsu, A., Woo, C. C., Yuan, Y., Tan, K. H. B., et al. (2018). Thymoquinone inhibits bone metastasis of breast cancer cells through abrogation of the CXCR4 signaling axis. Frontiers in Pharmacology, 9, 1294. https://doi.org/10.3389/fphar.2018.01294
Burits, M., & Bucar, F. (2000). Antioxidant activity of Nigella sativa essential oil. Phytotherapy Research, 14(5), 323–328. https://doi.org/10.1002/1099-1573(200008)14:5%3c323::Aid-Ptr621%3e3.0.Co;2-Q
Hajhashemi, V., Ghannadi, A., & Jafarabadi, H. (2004). Black cumin seed essential oil, as a potent analgesic and antiinflammatory drug. Phytotherapy Research, 18(3), 195–199. https://doi.org/10.1002/ptr.1390
Shanmugam, M. K., Arfuso, F., Kumar, A. P., Wang, L., Goh, B. C., Ahn, K. S., et al. (2018). Modulation of diverse oncogenic transcription factors by thymoquinone, an essential oil compound isolated from the seeds of Nigella sativa Linn. Pharmacological Research, 129, 357–364.
Woo, C. C., Loo, S. Y., Gee, V., Yap, C. W., Sethi, G., Kumar, A. P., et al. (2011). Anticancer activity of thymoquinone in breast cancer cells: Possible involvement of PPAR-γ pathway. Biochemical Pharmacology, 82(5), 464–475.
Huang, W. W., He, T. T., Chai, C. S., Yang, Y., Zheng, Y. H., Zhou, P., et al. (2012). Triptolide inhibits the proliferation of prostate cancer cells and down-regulates SUMO-specific protease 1 expression. Plos One, 7(5), ARTN e37693. https://doi.org/10.1371/journal.pone.0037693.
Liu, J., Jiang, Z., Xiao, J., Zhang, Y., Lin, S., Duan, W., et al. (2009). Effects of triptolide from Tripterygium wilfordii on ERalpha and p53 expression in two human breast cancer cell lines. Phytomedicine, 16(11), 1006–1013. https://doi.org/10.1016/j.phymed.2009.03.021
Li, L. H., Stanton, J. D., Tolson, A. H., Luo, Y., & Wang, H. B. (2009). Bioactive terpenoids and flavonoids from ginkgo biloba extract induce the expression of hepatic drug-metabolizing enzymes through pregnane X receptor, constitutive androstane receptor, and aryl hydrocarbon receptor-mediated pathways. Pharmaceutical Research, 26(4), 872–882. https://doi.org/10.1007/s11095-008-9788-8
Lakshmi, A., & Subramanian, S. (2014). Chemotherapeutic effect of tangeretin, a polymethoxylated flavone studied in 7, 12-dimethylbenz(a)anthracene induced mammary carcinoma in experimental rats. Biochimie, 99, 96–109. https://doi.org/10.1016/j.biochi.2013.11.017
Jia, Y., Hoang, M. H., Jun, H. J., Lee, J. H., & Lee, S. J. (2013). Cyanidin, a natural flavonoid, is an agonistic ligand for liver X receptor alpha and beta and reduces cellular lipid accumulation in macrophages and hepatocytes. Bioorganic & Medicinal Chemistry Letters, 23(14), 4185–4190. https://doi.org/10.1016/j.bmcl.2013.05.030
Tu, W. C., Wang, S. Y., Chien, S. C., Lin, F. M., Chen, L. R., Chiu, C. Y., et al. (2007). Diterpenes from Cryptomeria japonica inhibit androgen receptor transcriptional activity in prostate cancer cells. Planta Medica, 73(13), 1407–1409. https://doi.org/10.1055/s-2007-990233
Jacobs, M. N., Nolan, G. T., & Hood, S. R. (2005). Lignans, bacteriocides and organochlorine compounds activate the human pregnane X receptor (PXR). Toxicology and Applied Pharmacology, 209(2), 123–133. https://doi.org/10.1016/j.taap.2005.03.015
Hoang, M. H., Jia, Y., Jun, H. J., Lee, J. H., Lee, B. Y., & Lee, S. J. (2012). Fucosterol is a selective liver X receptor modulator that regulates the expression of key genes in cholesterol homeostasis in macrophages, hepatocytes, and intestinal cells. Journal of Agricultural and Food Chemistry, 60(46), 11567–11575. https://doi.org/10.1021/jf3019084
Hoang, M. H., Jia, Y., Jun, H. J., Lee, J. H., Lee, D. H., Hwang, B. Y., et al. (2012). Ethyl 2,4,6-trihydroxybenzoate is an agonistic ligand for liver X receptor that induces cholesterol efflux from macrophages without affecting lipid accumulation in HepG2 cells. Bioorganic & Medicinal Chemistry Letters, 22(12), 4094–4099. https://doi.org/10.1016/j.bmcl.2012.04.071
Jun, H. J., Hoang, M. H., Lee, J. W., Yaoyao, J., Lee, J. H., Lee, D. H., et al. (2012). Iristectorigenin B isolated from Belamcanda chinensis is a liver X receptor modulator that increases ABCA1 and ABCG1 expression in macrophage RAW 264.7 cells. Biotechnology Letters, 34(12), 2213–2221, https://doi.org/10.1007/s10529-012-1036-y.
Lin, H. R. (2013). Paeoniflorin acts as a liver X receptor agonist. Journal of Asian Natural Products Research, 15(1), 35–45. https://doi.org/10.1080/10286020.2012.742510
Kma, L. (2014). Plant extracts and plant-derived compounds: Promising players in countermeasure strategy against radiological exposure: A review. Asian Pacific Journal of Cancer Prevention, 15(6), 2405–2425.
Wentworth, J. M., Agostini, M., Love, J., Schwabe, J. W., & Chatterjee, V. K. (2000). St John’s wort, a herbal antidepressant, activates the steroid X receptor. Journal of Endocrinology, 166(3), R11-16. https://doi.org/10.1677/joe.0.166r011
Yang, Y., Ikezoe, T., Takeuchi, T., Adachi, Y., Ohtsuki, Y., Koeffler, H. P., et al. (2006). Zanthoxyli Fructus induces growth arrest and apoptosis of LNCaP human prostate cancer cells in vitro and in vivo in association with blockade of the AKT and AR signal pathways. Oncology Reports, 15(6), 1581–1590.
Yang, Y., Ikezoe, T., Zheng, Z., Taguchi, H., Koeffler, H. P., & Zhu, W. G. (2007). Saw Palmetto induces growth arrest and apoptosis of androgen-dependent prostate cancer LNCaP cells via inactivation of STAT 3 and androgen receptor signaling. International Journal of Oncology, 31(3), 593–600.
Chen, K. C., Peng, C. C., Chiu, W. T., Cheng, Y. T., Huang, G. T., Hsieh, C. L., et al. (2010). Action mechanism and signal pathways of Psidium guajava L. aqueous extract in killing prostate cancer LNCaP cells. Nutrition and Cancer, 62(2), 260–270, https://doi.org/10.1080/01635580903407130.
Mandal, A., & Bishayee, A. (2015). Mechanism of breast cancer preventive action of pomegranate: Disruption of estrogen receptor and Wnt/beta-catenin signaling pathways. Molecules, 20(12), 22315–22328. https://doi.org/10.3390/molecules201219853
He, Y. Q., Ma, G. Y., Peng, J. N., Ma, Z. Y., & Hamann, M. T. (2012). Liver X receptor and peroxisome proliferator-activated receptor agonist from Cornus alternifolia. Biochimica et Biophysica Acta, 1820(7), 1021–1026. https://doi.org/10.1016/j.bbagen.2012.02.004
Chen, J., Power, K. A., Mann, J., Cheng, A., & Thompson, L. U. (2007). Dietary flaxseed interaction with tamoxifen induced tumor regression in athymic mice with MCF-7 xenografts by downregulating the expression of estrogen related gene products and signal transduction pathways. Nutrition and Cancer, 58(2), 162–170. https://doi.org/10.1080/01635580701328271
Jeyabalan, J., Aqil, F., Munagala, R., Annamalai, L., Vadhanam, M. V., & Gupta, R. C. (2014). Chemopreventive and therapeutic activity of dietary blueberry against estrogen-mediated breast cancer. Journal of Agriculture and Food Chemistry, 62(18), 3963–3971. https://doi.org/10.1021/jf403734j
Nejati-Koshki, K., Akbarzadeh, A., & Pourhassan-Moghaddam, M. (2014). Curcumin inhibits leptin gene expression and secretion in breast cancer cells by estrogen receptors. Cancer Cell International, 14, 66. https://doi.org/10.1186/1475-2867-14-66
Hallman, K., Aleck, K., Dwyer, B., Lloyd, V., Quigley, M., Sitto, N., et al. (2017). The effects of turmeric (curcumin) on tumor suppressor protein (p53) and estrogen receptor (ERalpha) in breast cancer cells. Breast Cancer (Dove Med Press), 9, 153–161. https://doi.org/10.2147/BCTT.S125783
Sanaei, M., Kavoosi, F., & Arabloo, M. (2020). Effect of curcumin in comparison with trichostatin A on the reactivation of estrogen receptor alpha gene expression, cell growth inhibition and apoptosis induction in hepatocellular carcinoma Hepa 1–6 cell lline. Asian Pacific Journal of Cancer Prevention: APJCP, 21(4), 1045.
Sun, M., Estrov, Z., Ji, Y., Coombes, K. R., Harris, D. H., & Kurzrock, R. (2008). Curcumin (diferuloylmethane) alters the expression profiles of microRNAs in human pancreatic cancer cells. Molecular Cancer Therapeutics, 7(3), 464–473. https://doi.org/10.1158/1535-7163.MCT-07-2272
Nakamura, K., Yasunaga, Y., Segawa, T., Ko, D., Moul, J. W., Srivastava, S., et al. (2002). Curcumin down-regulates AR gene expression and activation in prostate cancer cell lines. International Journal of Oncology, 21(4), 825–830.
Choi, H., Lim, J., & Hong, J. (2010). Curcumin interrupts the interaction between the androgen receptor and Wnt/β-catenin signaling pathway in LNCaP prostate cancer cells. Prostate Cancer and Prostatic Diseases, 13(4), 343–349.
Zhang, H. N., Yu, C. X., Zhang, P. J., Chen, W. W., Jiang, A. L., Kong, F., et al. (2007). Curcumin downregulates homeobox gene NKX3.1 in prostate cancer cell LNCaP.Acta Pharmacologica Sinica, 28(3), 423–430, https://doi.org/10.1111/j.1745-7254.2007.00501.x.
Guo, H., Xu, Y. M., Ye, Z. Q., Yu, J. H., & Hu, X. Y. (2013). Curcumin induces cell cycle arrest and apoptosis of prostate cancer cells by regulating the expression of IkappaBalpha, c-Jun and androgen receptor. Die Pharmazie, 68(6), 431–434.
Dorai, T., Gehani, N., & Katz, A. (2000). Therapeutic potential of curcumin in human prostate cancer - I. curcumin induces apoptosis in both androgen-dependent and androgen-independent prostate cancer cells. Prostate Cancer and Prostatic Diseases, 3(2), 84–93, https://doi.org/10.1038/sj.pcan.4500399.
Thangapazham, R. L., Shaheduzzaman, S., Kim, K. H., Passi, N., Tadese, A., Vahey, M., et al. (2008). Androgen responsive and refractory prostate cancer cells exhibit distinct curcumin regulated transcriptome. Cancer Biology & Therapy, 7(9), 1427–1435. https://doi.org/10.4161/cbt.7.9.6469
Yallapu, M. M., Khan, S., Maher, D. M., Ebeling, M. C., Sundram, V., Chauhan, N., et al. (2014). Anti-cancer activity of curcumin loaded nanoparticles in prostate cancer. Biomaterials, 35(30), 8635–8648. https://doi.org/10.1016/j.biomaterials.2014.06.040
Sharma, V., Kumar, L., Mohanty, S. K., Maikhuri, J. P., Rajender, S., & Gupta, G. (2016). Sensitization of androgen refractory prostate cancer cells to anti androgens through re-expression of epigenetically repressed androgen receptor - Synergistic action of quercetin and curcumin. Molecular and Cellular Endocrinology, 431(C), 12–23, https://doi.org/10.1016/j.mce.2016.04.024.
Narayanan, N. K., Nargi, D., Randolph, C., & Narayanan, B. A. (2009). Liposome encapsulation of curcumin and resveratrol in combination reduces prostate cancer incidence in PTEN knockout mice. International Journal of Cancer, 125(1), 1–8. https://doi.org/10.1002/ijc.24336
Pham, N. K., Bui, H. T., Tran, T. H., Hoang, T. N. A., Vu, T. H., Do, D. T., et al. (2021). Dammarane triterpenes and phytosterols from Dysoxylum tpongense Pierre and their anti-inflammatory activity against liver X receptors and NF-κB activation. Steroids, 175, 108902.
Schleich, S., Papaioannou, M., Baniahmad, A., & Matusch, R. (2006). Activity-guided isolation of an antiandrogenic compound of Pygeum africanum. Planta medica, 72(06), 547–551.
Levenson, A. S., Gehm, B. D., Pearce, S. T., Horiguchi, J., Simons, L. A., Ward, J. E., et al. (2003). Resveratrol acts as an estrogen receptor (ER) agonist in breast cancer cells stably transfected with ER alpha. International Journal of Cancer, 104(5), 587–596. https://doi.org/10.1002/ijc.10992
Mitchell, S. H., Zhu, W., & Young, C. Y. F. (1999). Resveratrol inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells. Cancer Research, 59(23), 5892–5895.
Wang, Y., Romigh, T., He, X., Orloff, M. S., Silverman, R. H., Heston, W. D., et al. (2010). Resveratrol regulates the PTEN/AKT pathway through androgen receptor-dependent and -independent mechanisms in prostate cancer cell lines. Human Molecular Genetics, 19(22), 4319–4329. https://doi.org/10.1093/hmg/ddq354
Harada, N., Murata, Y., Yamaji, R., Miura, T., Inui, H., & Nakano, Y. (2007). Resveratrol down-regulates the androgen receptor at the post-translational level in prostate cancer cells. Journal of Nutritional Science and Vitaminology, 53(6), 556–560. https://doi.org/10.3177/jnsv.53.556
Mitani, T., Harada, N., Tanimori, S., Nakano, Y., Inui, H., & Yamaji, R. (2014). Resveratrol inhibits hypoxia-inducible factor-1alpha-mediated androgen receptor signaling and represses tumor progression in castration-resistant prostate cancer. Journal of Nutritional Science and Vitaminology (Tokyo), 60(4), 276–282.
Ye, M., Tian, H., Lin, S., Mo, J., Li, Z., Chen, X., et al. (2020). Resveratrol inhibits proliferation and promotes apoptosis via the androgen receptor splicing variant 7 and PI3K/AKT signaling pathway in LNCaP prostate cancer cells. Oncology Letters, 20(5), 169. https://doi.org/10.3892/ol.2020.12032
Qi, H. Y., Jiang, Z. Y., Wang, C. Q., Yang, Y., Li, L., He, H., et al. (2017). Sensitization of tamoxifen-resistant breast cancer cells by Z-ligustilide through inhibiting autophagy and accumulating DNA damages. Oncotarget, 8(17), 29300–29317, https://doi.org/10.18632/oncotarget.16832.
Shrestha, R., Mohankumar, K., & Safe, S. (2020). Bis-indole derived nuclear receptor 4A1 (NR4A1) antagonists inhibit TGFβ-induced invasion of embryonal rhabdomyosarcoma cells. American Journal of Cancer Research, 10(8), 2495.
Yeh, S.-L., Yeh, C.-L., Chan, S.-T., & Chuang, C.-H. (2011). Plasma rich in quercetin metabolites induces G2/M arrest by upregulating PPAR-γ expression in human A549 lung cancer cells. Planta Medica, 77(10), 992–998.
Krausova, L., Stejskalova, L., Wang, H., Vrzal, R., Dvorak, Z., Mani, S., et al. (2011). Metformin suppresses pregnane X receptor (PXR)-regulated transactivation of CYP3A4 gene. Biochemical Pharmacology, 82(11), 1771–1780. https://doi.org/10.1016/j.bcp.2011.08.023
Helleboid, S., Haug, C., Lamottke, K., Zhou, Y., Wei, J., Daix, S., et al. (2014). The identification of naturally occurring neoruscogenin as a bioavailable, potent, and high-affinity agonist of the nuclear receptor RORα (NR1F1). Journal of Biomolecular Screening, 19(3), 399–406.
Ao, M., Zhang, J., Qian, Y., Li, B., Wang, X., Chen, J., et al. (2022). Design and synthesis of adamantyl-substituted flavonoid derivatives as anti-inflammatory Nur77 modulators: Compound B7 targets Nur77 and improves LPS-induced inflammation in vitro and in vivo. Bioorganic Chemistry, 120, 105645.
Zhao, J., Khan, S. I., Wang, M., Vasquez, Y., Yang, M. H., Avula, B., et al. (2014). Octulosonic acid derivatives from Roman chamomile (Chamaemelum nobile) with activities against inflammation and metabolic disorder. Journal of Natural Products, 77(3), 509–515.
Tamehiro, N., Sato, Y., Suzuki, T., Hashimoto, T., Asakawa, Y., Yokoyama, S., et al. (2005). Riccardin C: A natural product that functions as a liver X receptor (LXR) α agonist and an LXRβ antagonist. FEBS Letters, 579(24), 5299–5304.
Uemura, T., Goto, T., Kang, M. S., Mizoguchi, N., Hirai, S., Lee, J. Y., et al. (2011). Diosgenin, the main aglycon of fenugreek, inhibits LXRα activity in HepG2 cells and decreases plasma and hepatic triglycerides in obese diabetic mice. The Journal of Nutrition, 141(1), 17–23.
Goldwasser, J., Cohen, P. Y., Yang, E., Balaguer, P., Yarmush, M. L., & Nahmias, Y. (2010). Transcriptional regulation of human and rat hepatic lipid metabolism by the grapefruit flavonoid naringenin: Role of PPARα PPARγ and LXRα. PloS One, 5(8), e12399.
Sheng, X., Wang, M., Lu, M., Xi, B., Sheng, H., & Zang, Y. Q. (2011). Rhein ameliorates fatty liver disease through negative energy balance, hepatic lipogenic regulation, and immunomodulation in diet-induced obese mice. American Journal of Physiology-Endocrinology and Metabolism, 300(5), E886–E893.
Montserrat-de la Paz, S., Fernández-Arche, M., Bermúdez, B., & García-Giménez, M. D. (2015). The sterols isolated from evening primrose oil inhibit human colon adenocarcinoma cell proliferation and induce cell cycle arrest through upregulation of LXR. Journal of Functional Foods, 12, 64–69.
Kao, T.-C., Shyu, M.-H., & Yen, G.-C. (2010). Glycyrrhizic acid and 18β-glycyrrhetinic acid inhibit inflammation via PI3K/Akt/GSK3β signaling and glucocorticoid receptor activation. Journal of Agricultural and Food Chemistry, 58(15), 8623–8629.
Kao, T.-C., Wu, C.-H., & Yen, G.-C. (2013). Glycyrrhizic acid and 18β-glycyrrhetinic acid recover glucocorticoid resistance via PI3K-induced AP1 CRE and NFAT activation. Phytomedicine, 20(3–4), 295–302.
Chintharlapalli, S., Papineni, S., Jutooru, I., McAlees, A., & Safe, S. (2007). Structure-dependent activity of glycyrrhetinic acid derivatives as peroxisome proliferator–activated receptor γ agonists in colon cancer cells. Molecular Cancer Therapeutics, 6(5), 1588–1598.
Lee, Y., Chung, E., Lee, K. Y., Lee, Y. H., Huh, B., & Lee, S. K. (1997). Ginsenoside-Rg1, one of the major active molecules from Panax ginseng, is a functional ligand of glucocorticoid receptor. Molecular and Cellular Endocrinology, 133(2), 135–140.
Ferron, P.-J., Hogeveen, K., De Sousa, G., Rahmani, R., Dubreil, E., Fessard, V. r., et al. (2016). Modulation of CYP3A4 activity alters the cytotoxicity of lipophilic phycotoxins in human hepatic HepaRG cells. Toxicology in Vitro, 33, 136-146.
Cui, K., Wu, H., Li, Z., Li, H., Yang, R., Guo, H., et al. (2021). Ferulic acid and P-coumaric acid inhibit colon cancer growth through GR/lncRNA 495810/PKM2 mediated aerobic glycolysis. Available at SSRN 3844821. https://doi.org/10.2139/ssrn.3844821
Gasmi, J., & Sanderson, J. T. (2010). Growth inhibitory, antiandrogenic, and pro-apoptotic effects of punicic acid in LNCaP human prostate cancer cells. Journal of Agricultural and Food Chemistry, 58(23), 12149–12156.
Cvoro, A., Paruthiyil, S., Jones, J. O., Tzagarakis-Foster, C., Clegg, N. J., Tatomer, D., et al. (2007). Selective activation of estrogen receptor-β transcriptional pathways by an herbal extract. Endocrinology, 148(2), 538–547.
Liu, L., Ma, H., Tang, Y., Chen, W., Lu, Y., Guo, J., et al. (2012). Discovery of estrogen receptor α modulators from natural compounds in Si-Wu-Tang series decoctions using estrogen-responsive MCF-7 breast cancer cells. Bioorganic & Medicinal Chemistry Letters, 22(1), 154–163.
Huang, T.H.-W., Razmovski-Naumovski, V., Salam, N. K., Duke, R. K., Duke, C. C., & Roufogalis, B. D. (2005). A novel LXR-α activator identified from the natural product Gynostemma pentaphyllum. Biochemical Pharmacology, 70(9), 1298–1308.
Yuan, H.-Q., Kong, F., Wang, X.-L., Young, C. Y., Hu, X.-Y., & Lou, H.-X. (2008). Inhibitory effect of acetyl-11-keto-β-boswellic acid on androgen receptor by interference of Sp1 binding activity in prostate cancer cells. Biochemical Pharmacology, 75(11), 2112–2121.
Chung, B. H., Lee, H.-Y., Lee, J. S., & Young, C. Y. (2006). Perillyl alcohol inhibits the expression and function of the androgen receptor in human prostate cancer cells. Cancer Letters, 236(2), 222–228.
Pathirana, C., Stein, R. B., Berger, T. S., Fenical, W., Ianiro, T., Mais, D. E., et al. (1995). Nonsteroidal human progesterone receptor modulators from the marine alga Cymopolia barbata. Molecular Pharmacology, 47(3), 630–635.
Zhao, Z., Wang, L., James, T., Jung, Y., Kim, I., Tan, R., et al. (2015). Reciprocal regulation of ERα and ERβ stability and activity by diptoindonesin G. Chemistry & Biology, 22(12), 1608–1621.
Lin, W., Huang, J., Liao, X., Yuan, Z., Feng, S., Xie, Y., et al. (2016). Neo-tanshinlactone selectively inhibits the proliferation of estrogen receptor positive breast cancer cells through transcriptional down-regulation of estrogen receptor alpha. Pharmacological Research, 111, 849–858.
Onogi, K., Niwa, K., Tang, L., Yun, W., Mori, H., & Tamaya, T. (2006). Inhibitory effects of Hochu-ekki-to on endometrial carcinogenesis induced by N-methyl-N-nitrosourea and 17β-estradiol in mice. Oncology Reports, 16(6), 1343–1348.
Marconett, C. N., Morgenstern, T. J., San Roman, A. K., Sundar, S. N., Singhal, A. K., & Firestone, G. L. (2010). BZL101, a phytochemical extract from the Scutellaria barbata plant, disrupts proliferation of human breast and prostate cancer cells through distinct mechanisms dependent on the cancer cell phenotype. Cancer Biology & Therapy, 10(4), 397–405.
Mora, F. D., Jones, D. K., Desai, P. V., Patny, A., Avery, M. A., Feller, D. R., et al. (2006). Bioassay for the identification of natural product-based activators of peroxisome proliferator-activated receptor-gamma (PPARgamma): The marine sponge metabolite psammaplin A activates PPARgamma and induces apoptosis in human breast tumor cells. Journal of Natural Products, 69(4), 547–552. https://doi.org/10.1021/np050397q
Sadar, M. D., Williams, D. E., Mawji, N. R., Patrick, B. O., Wikanta, T., Chasanah, E., et al. (2008). Sintokamides A to E, chlorinated peptides from the sponge Dysidea sp that inhibit transactivation of the N-terminus of the androgen receptor in prostate cancer cells. Organic Letters, 10(21), 4947–4950. https://doi.org/10.1021/ol802021w
Festa, C., De Marino, S., D’Auria, M. V., Bifulco, G., Renga, B., Fiorucci, S., et al. (2011). Solomonsterols A and B from Theonella swinhoei. The first example of C-24 and C-23 sulfated sterols from a marine source endowed with a PXR agonistic activity. Journal of Medicinal Chemistry, 54(1), 401–405, https://doi.org/10.1021/jm100968b.
Sepe, V., Ummarino, R., D’Auria, M. V., Mencarelli, A., D’Amore, C., Renga, B., et al. (2011). Total synthesis and pharmacological characterization of solomonsterol A, a potent marine pregnane-X-receptor agonist endowed with anti-inflammatory activity. Journal of Medicinal Chemistry, 54(13), 4590–4599. https://doi.org/10.1021/jm200241s
Sepe, V., Ummarino, R., D'Auria, M. V., Lauro, G., Bifulco, G., D'Amore, C., et al. (2012). Modification in the side chain of solomonsterol A: discovery of cholestan disulfate as a potent pregnane-X-receptor agonist. Organic & Biomolecular Chemistry, 10(31), 6350-6362, doi:10.1039/c2ob25800e.
De Marino, S., Ummarino, R., D’Auria, M. V., Chini, M. G., Bifulco, G., Renga, B., et al. (2011). Theonellasterols and conicasterols from Theonella swinhoei. Novel marine natural ligands for human nuclear receptors. Journal of Medicinal Chemistry, 54(8), 3065–3075, https://doi.org/10.1021/jm200169t.
Renga, B., Mencarelli, A., D’Amore, C., Cipriani, S., D’Auria, M. V., Sepe, V., et al. (2012). Discovery that theonellasterol a marine sponge sterol is a highly selective FXR antagonist that protects against liver injury in cholestasis. PloS One, 7(1), ARTN e30443. https://doi.org/10.1371/journal.pone.0030443.
Sepe, V., Ummarino, R., D’Auria, M. V., Taglialatela-Scafati, O., De Marino, S., D’Amore, C., et al. (2012). Preliminary structure-activity relationship on theonellasterol, a new chemotype of FXR antagonist, from the marine sponge Theonella swinhoei. Marine Drugs, 10(11), 2448–2466. https://doi.org/10.3390/md10112448
Sepe, V., Ummarino, R., D’Auria, M. V., Chini, M. G., Bifulco, G., Renga, B., et al. (2012). Conicasterol E, a small heterodimer partner sparing farnesoid X receptor modulator endowed with a pregnane X receptor agonistic activity, from the marine sponge Theonella swinhoei. Journal of Medicinal Chemistry, 55(1), 84–93. https://doi.org/10.1021/jm201004p
Chini, M. G., Jones, C. R., Zampella, A., D’Auria, M. V., Renga, B., Fiorucci, S., et al. (2012). Quantitative NMR-derived interproton distances combined with quantum mechanical calculations of 13C chemical shifts in the stereochemical determination of conicasterol F, a nuclear receptor ligand from Theonella swinhoei. Journal of Organic Chemistry, 77(3), 1489–1496. https://doi.org/10.1021/jo2023763
De Marino, S., Sepe, V., D'Auria, M. V., Bifulco, G., Renga, B., Petek, S., et al. (2011). Towards new ligands of nuclear receptors. Discovery of malaitasterol A, an unique bis-secosterol from marine sponge Theonella swinhoei. Organic & Biomolecular Chemistry, 9(13), 4856–4862, https://doi.org/10.1039/c1ob05378g.
De Marino, S., Ummarino, R., D’Auria, M. V., Chini, M. G., Bifulco, G., D’Amore, C., et al. (2012). 4-Methylenesterols from Theonella swinhoei sponge are natural pregnane-X-receptor agonists and farnesoid-X-receptor antagonists that modulate innate immunity. Steroids, 77(5), 484–495. https://doi.org/10.1016/j.steroids.2012.01.006
Sepe, V., D’Amore, C., Ummarino, R., Renga, B., D’Auria, M. V., Novellino, E., et al. (2014). Insights on pregnane-X-receptor modulation. Natural and semisynthetic steroids from Theonella marine sponges. European Journal of Medicinal Chemistry, 73, 126–134. https://doi.org/10.1016/j.ejmech.2013.12.005
Festa, C., Lauro, G., De Marino, S., D’Auria, M. V., Monti, M. C., Casapullo, A., et al. (2012). Plakilactones from the marine sponge Plakinastrella mamillaris. Discovery of a new class of marine ligands of peroxisome proliferator-activated receptor γ. Journal of Medicinal Chemistry, 55(19), 8303–8317.
Festa, C., D’Amore, C., Renga, B., Lauro, G., De Marino, S., D’Auria, M. V., et al. (2013). Oxygenated polyketides from Plakinastrella mamillaris as a new chemotype of PXR agonists. Marine Drugs, 11(7), 2314–2327. https://doi.org/10.3390/md11072314
Chianese, G., Sepe, V., Limongelli, V., Renga, B., D’Amore, C., Zampella, A., et al. (2014). Incisterols, highly degraded marine sterols, are a new chemotype of PXR agonists. Steroids, 83, 80–85. https://doi.org/10.1016/j.steroids.2014.02.003
Meimetis, L. G., Williams, D. E., Mawji, N. R., Banuelos, C. A., Lal, A. A., Park, J. J., et al. (2012). Niphatenones, glycerol ethers from the sponge Niphates digitalis block androgen receptor transcriptional activity in prostate cancer cells: Structure elucidation, synthesis, and biological activity. Journal of Medicinal Chemistry, 55(1), 503–514. https://doi.org/10.1021/jm2014056
Wang, S. S., Wang, Z., Lin, S. C., Zheng, W. L., Wang, R., Jin, S. K., et al. (2012). Revealing a natural marine product as a novel agonist for retinoic acid receptors with a unique binding mode and inhibitory effects on cancer cells. Biochemical Journal, 446, 79–87. https://doi.org/10.1042/Bj20120726
Di Leva, F. S., Festa, C., D’Amore, C., De Marino, S., Renga, B., D’Auria, M. V., et al. (2013). Binding mechanism of the farnesoid X receptor marine antagonist suvanine reveals a strategy to forestall drug modulation on nuclear receptors. Design, synthesis, and biological evaluation of novel ligands. Journal of Medicinal Chemistry, 56(11), 4701–4717, https://doi.org/10.1021/jm400419e.
Zhou, M., Peng, B. R., Tian, W., Su, J. H., Wang, G., Lin, T., et al. (2020). 12-Deacetyl-12-epi-scalaradial, a scalarane sesterterpenoid from a marine sponge Hippospongia sp., induces HeLa cells apoptosis via MAPK/ERK pathway and modulates nuclear receptor Nur77. Marine Drugs, 18(7), 375. https://doi.org/10.3390/md18070375
Wu, Y., Liao, H., Liu, L.-Y., Sun, F., Chen, H.-F., Jiao, W.-H., et al. (2020). Phakefustatins A-C: Kynurenine-bearing cycloheptapeptides as RXRα modulators from the marine sponge Phakellia fusca. Organic Letters, 22(17), 6703–6708.
Machida, K., Abe, T., Arai, D., Okamoto, M., Shimizu, I., de Voogd, N. J., et al. (2014). Cinanthrenol A, an estrogenic steroid containing phenanthrene nucleus, from a marine sponge Cinachyrella sp. Organic Letters, 16(6), 1539–1541.
Parrish, S. M., Neupane, R. P., Harper, M. K., Head, J., & Williams, P. G. (2019). Myrmenaphthol A, isolated from a Hawaiian sponge of the genus Myrmekioderma. Journal of Natural Products, 82(9), 2668–2671. https://doi.org/10.1021/acs.jnatprod.9b00665
Imperatore, C., D’Aniello, F., Aiello, A., Fiorucci, S., D’Amore, C., Sepe, V., et al. (2014). Phallusiasterols A and B: Two new sulfated sterols from the Mediterranean tunicate Phallusia fumigata and their effects as modulators of the PXR receptor. Marine Drugs, 12(4), 2066–2078. https://doi.org/10.3390/md12042066
Imperatore, C., Senese, M., Aiello, A., Luciano, P., Fiorucci, S., D’Amore, C., et al. (2016). Phallusiasterol C, A new disulfated steroid from the Mediterranean Tunicate Phallusia fumigata. Marine Drugs, 14(6), 117. https://doi.org/10.3390/md14060117
Fidler, A. E., Holland, P. T., Reschly, E. J., Ekins, S., & Krasowski, M. D. (2012). Activation of a tunicate (Ciona intestinalis) xenobiotic receptor orthologue by both natural toxins and synthetic toxicants. Toxicon, 59(2), 365–372. https://doi.org/10.1016/j.toxicon.2011.12.008
Mensah-Osman, E., Lin, H.-L., Reinke, D., Hollenberg, P., & Baker, L. (2005). Ecteinascidin-743 is a potent inhibitor of P450 3A4 enzyme and accumulates cytoplasmic PXR to inhibit transcription of P450 3A4 and MDR1: Implications for the enhancement of cytotoxicity to chemotherapeutic agents in osteosarcoma. Journal of Clinical Oncology, 23(16_suppl), 9026–9026.
Sepe, V., Di Leva, F. S., D’Amore, C., Festa, C., De Marino, S., Renga, B., et al. (2014). Marine and semi-synthetic hydroxysteroids as new scaffolds for pregnane X receptor modulation. Marine Drugs, 12(6), 3091–3115. https://doi.org/10.3390/md12063091
Sepe, V., Bifulco, G., Renga, B., D’Amore, C., Fiorucci, S., & Zampella, A. (2011). Discovery of sulfated sterols from marine invertebrates as a new class of marine natural antagonists of farnesoid-X-receptor. Journal of Medicinal Chemistry, 54(5), 1314–1320. https://doi.org/10.1021/jm101336m
Popolo, A., Piccinelli, A. L., Morello, S., Sorrentino, R., Osmany, C. R., Rastrelli, L., et al. (2011). Cytotoxic activity of nemorosone in human MCF-7 breast cancer cells. Canadian Journal of Physiology and Pharmacology, 89(1), 50–57. https://doi.org/10.1139/y10-100
Moutsatsou, P., Papoutsi, Z., Kassi, E., Heldring, N., Zhao, C. Y., Tsiapara, A., et al. (2010). Fatty acids derived from royal jelly are modulators of estrogen receptor functions. PloS One, 5(12), ARTN e15594. https://doi.org/10.1371/journal.pone.0015594.
Zhao, Z., Hong, W., Zeng, Z., Wu, Y., Hu, K., Tian, X., et al. (2012). Mucroporin-M1 inhibits hepatitis B virus replication by activating the mitogen-activated protein kinase (MAPK) pathway and down-regulating HNF4alpha in vitro and in vivo. Journal of Biological Chemistry, 287(36), 30181–30190. https://doi.org/10.1074/jbc.M112.370312
Deng, Z., Zheng, L. F., Xie, X. W., Wei, H. K., & Peng, J. (2020). GPA peptide enhances Nur77 expression in intestinal epithelial cells to exert a protective effect against DSS-induced colitis. The Faseb Journal, 34(11), 15364–15378. https://doi.org/10.1096/fj.202000391RR
Ricote, M., Li, A. C., Willson, T. M., Kelly, C. J., & Glass, C. K. (1998). The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature, 391(6662), 79–82. https://doi.org/10.1038/34178
Shiraki, T., Kamiya, N., Shiki, S., Kodama, T. S., Kakizuka, A., & Jingami, H. (2005). α, β-unsaturated ketone is a core moiety of natural ligands for covalent binding to peroxisome proliferator-activated receptor γ. Journal of Biological Chemistry, 280(14), 14145–14153.
Shappell, S. B., Gupta, R. A., Manning, S., Whitehead, R., Boeglin, W. E., Schneider, C., et al. (2001). 15S-Hydroxyeicosatetraenoic acid activates peroxisome proliferator-activated receptor gamma and inhibits proliferation in PC3 prostate carcinoma cells. Cancer Research, 61(2), 497–503.
Pettersson, F., Dalgleish, A. G., Bissonnette, R. P., & Colston, K. W. (2002). Retinoids cause apoptosis in pancreatic cancer cells via activation of RAR-gamma and altered expression of Bcl-2/Bax. British Journal of Cancer, 87(5), 555–561. https://doi.org/10.1038/sj.bjc.6600496
Campbell, S. E., Stone, W. L., Whaley, S. G., Qui, M., & Krishnan, K. (2003). Gamma (gamma) tocopherol upregulates peroxisome proliferator activated receptor (PPAR) gamma (gamma) expression in SW 480 human colon cancer cell lines. BMC Cancer, 3, 25. https://doi.org/10.1186/1471-2407-3-25
Kinjo, J., Tsuchihashi, R., Morito, K., Hirose, T., Aomori, T., Nagao, T., et al. (2004). Interactions of phytoestrogens with estrogen receptors alpha and beta (III). Estrogenic activities of soy isoflavone aglycones and their metabolites isolated from human urine. Biological & Pharmaceutical Bulletin, 27(2), 185–188, https://doi.org/10.1248/bpb.27.185.
Maggiora, M., Bologna, M., Ceru, M. P., Possati, L., Angelucci, A., Cimini, A., et al. (2004). An overview of the effect of linoleic and conjugated-linoleic acids on the growth of several human tumor cell lines. International Journal of Cancer, 112(6), 909–919. https://doi.org/10.1002/ijc.20519
Kuniyasu, H., Yoshida, K., Sasaki, T., Sasahira, T., Fujii, K., & Ohmori, H. (2006). Conjugated linoleic acid inhibits peritoneal metastasis in human gastrointestinal cancer cells. International Journal of Cancer, 118(3), 571–576. https://doi.org/10.1002/ijc.21368
Evans, N. P., Misyak, S. A., Schmelz, E. M., Guri, A. J., Hontecillas, R., & Bassaganya-Riera, J. (2010). Conjugated linoleic acid ameliorates inflammation-induced colorectal cancer in mice through activation of PPARγ. The Journal of Nutrition, 140(3), 515–521.
Sun, H., Berquin, I. M., & Edwards, I. J. (2005). Omega-3 polyunsaturated fatty acids regulate syndecan-1 expression in human breast cancer cells. Cancer Research, 65(10), 4442–4447. https://doi.org/10.1158/0008-5472.CAN-04-4200
Sun, H., Berquin, I. M., Owens, R. T., O’Flaherty, J. T., & Edwards, I. J. (2008). Peroxisome proliferator-activated receptor gamma-mediated up-regulation of syndecan-1 by n-3 fatty acids promotes apoptosis of human breast cancer cells. Cancer Research, 68(8), 2912–2919. https://doi.org/10.1158/0008-5472.CAN-07-2305
Edwards, I. J., Sun, H., Hu, Y., Berquin, I. M., O’Flaherty, J. T., Cline, J. M., et al. (2008). In vivo and in vitro regulation of syndecan 1 in prostate cells by n-3 polyunsaturated fatty acids. Journal of Biological Chemistry, 283(26), 18441–18449. https://doi.org/10.1074/jbc.M802107200
Lampen, A., Leifheit, M., Voss, J., & Nau, H. (2005). Molecular and cellular effects of cis-9, trans-11-conjugated linoleic acid in enterocytes: Effects on proliferation, differentiation, and gene expression. Biochimica et Biophysica Acta, 1735(1), 30–40. https://doi.org/10.1016/j.bbalip.2005.01.007
Kameue, C., Tsukahara, T., & Ushida, K. (2006). Alteration of gene expression in the colon of colorectal cancer model rat by dietary sodium gluconate. Bioscience Biotechnology and Biochemistry, 70(3), 606–614. https://doi.org/10.1271/bbb.70.606
Zand, H., Rhimipour, A., Bakhshayesh, M., Shafiee, M., Nour Mohammadi, I., & Salimi, S. (2007). Involvement of PPAR-gamma and p53 in DHA-induced apoptosis in Reh cells. Molecular and Cellular Biochemistry, 304(1–2), 71–77. https://doi.org/10.1007/s11010-007-9487-5
Lee, H. J., Ju, J., Paul, S., So, J. Y., DeCastro, A., Smolarek, A., et al. (2009). Mixed tocopherols prevent mammary tumorigenesis by inhibiting estrogen action and activating PPAR-gamma. Clinical Cancer Research, 15(12), 4242–4249. https://doi.org/10.1158/1078-0432.CCR-08-3028
Smolarek, A. K., So, J. Y., Burgess, B., Kong, A.-N.T., Reuhl, K., Lin, Y., et al. (2012). Dietary administration of δ-and γ-tocopherol inhibits tumorigenesis in the animal model of estrogen receptor–positive, but not HER-2 breast cancer. Cancer Prevention Research, 5(11), 1310–1320.
Smolarek, A. K., So, J. Y., Thomas, P. E., Lee, H. J., Paul, S., Dombrowski, A., et al. (2013). Dietary tocopherols inhibit cell proliferation, regulate expression of ERalpha, PPARgamma, and Nrf2, and decrease serum inflammatory markers during the development of mammary hyperplasia. Molecular Carcinogenesis, 52(7), 514–525. https://doi.org/10.1002/mc.21886
Yang, L., Yuan, J., Liu, L., Shi, C., Wang, L., Tian, F., et al. (2013). α-linolenic acid inhibits human renal cell carcinoma cell proliferation through PPAR-γ activation and COX-2 inhibition. Oncology Letters, 6(1), 197–202.
Attia, Y. M., Tawfiq, R. A., Ali, A. A., & Elmazar, M. M. (2017). The FXR agonist, obeticholic acid, suppresses HCC proliferation & metastasis: Role of IL-6/STAT3 signalling pathway. Science and Reports, 7(1), 12502. https://doi.org/10.1038/s41598-017-12629-4
Fang, H., Zhang, J., Ao, M., He, F., Chen, W., Qian, Y., et al. (2020). Synthesis and discovery of ω-3 polyunsaturated fatty acid-alkanolamine (PUFA-AA) derivatives as anti-inflammatory agents targeting Nur77. Bioorganic Chemistry, 105, 104456.
Tabata, Y., Iizuka, Y., Kashiwa, J., Masuda, N. T., Shinei, R., Kurihara, K.-I., et al. (2001). Fungal metabolites, PF1092 compounds and their derivatives, are nonsteroidal and selective progesterone receptor modulators. European Journal of Pharmacology, 430(2–3), 159–165.
Muthyala, R. S., Ju, Y. H., Sheng, S. B., Williams, L. D., Doerge, D. R., Katzenellenbogen, B. S., et al. (2004). Equol, a natural estrogenic metabolite from soy isoflavones: Convenient preparation and resolution of R- and S-equols and their differing binding and biological activity through estrogen receptors alpha and beta. Bioorganic & Medicinal Chemistry, 12(6), 1559–1567. https://doi.org/10.1016/j.bmc.2003.11.035
Zheng, W., Zhang, Y., Ma, D., Li, G., & Wang, P. (2011). Anti-invasion effects of R- and S-enantiomers of equol on prostate cancer PC3, DU145 cells. Wei Sheng Yan Jiu, 40(4), 423–425, 430.
Kelly, D., Campbell, J. I., King, T. P., Grant, G., Jansson, E. A., Coutts, A. G., et al. (2004). Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-gamma and RelA. Nature Immunology, 5(1), 104–112. https://doi.org/10.1038/ni1018
Lee, S. K., Kim, H. J., Chi, S. G., Jang, J. Y., Nam, K. D., Kim, N. H., et al. (2005). Saccharomyces boulardii activates expression of peroxisome proliferator-activated receptor-gamma in HT-29 cells. The Korean Journal of Gastroenterology, 45(5), 328–334.
Zhan, Y. P., Du, X. P., Chen, H. Z., Liu, J. J., Zhao, B. X., Huang, D. H., et al. (2008). Cytosporone B is an agonist for nuclear orphan receptor Nur77. Nature Chemical Biology, 4(9), 548–556. https://doi.org/10.1038/nchembio.106
Zaidman, B. Z., Wasser, S. P., Nevo, E., & Mahajna, J. (2008). Coprinus comatus and Ganoderma lucidum interfere with androgen receptor function in LNCaP prostate cancer cells. Molecular Biology Reports, 35(2), 107–117. https://doi.org/10.1007/s11033-007-9059-5
Moon, H. S., Lim, H., Moon, S., Oh, H. L., Kim, Y. T., Kim, M. K., et al. (2009). Benzyldihydroxyoctenone, a novel anticancer agent, induces apoptosis via mitochondrial-mediated pathway in androgen-sensitive LNCaP prostate cancer cells. Bioorganic & Medicinal Chemistry Letters, 19(3), 742–744. https://doi.org/10.1016/j.bmcl.2008.12.029
Venkatesh, M., Mukherjee, S., Wang, H., Li, H., Sun, K., Benechet, A. P., et al. (2014). Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. Immunity, 41(2), 296–310. https://doi.org/10.1016/j.immuni.2014.06.014
Meng, J., Fan, Y., Su, M., Chen, C., Ren, T., Wang, J., et al. (2014). WLIP derived from Lasiosphaera fenzlii Reich exhibits anti-tumor activity and induces cell cycle arrest through PPAR-γ associated pathways. International Immunopharmacology, 19(1), 37–44.
Byndloss, M. X., Olsan, E. E., Rivera-Chavez, F., Tiffany, C. R., Cevallos, S. A., Lokken, K. L., et al. (2017). Microbiota-activated PPAR-gamma signaling inhibits dysbiotic Enterobacteriaceae expansion. Science, 357(6351), 570–575. https://doi.org/10.1126/science.aam9949
Xie, C. L., Zhang, D., Xia, J. M., Hu, C. C., Lin, T., Lin, Y. K., et al. (2019). Steroids from the deep-sea-derived fungus Penicillium granulatum MCCC 3A00475 induced apoptosis via retinoid X receptor (RXR)-alpha pathway. Marine Drugs, 17(3), 178. https://doi.org/10.3390/md17030178
Khan, I., Huang, G., Li, X.-A., Liao, W., Leong, W. K., Xia, W., et al. (2019). Mushroom polysaccharides and jiaogulan saponins exert cancer preventive effects by shaping the gut microbiota and microenvironment in ApcMin/+ mice. Pharmacological Research, 148, 104448.
Dvorak, Z., Kopp, F., Costello, C. M., Kemp, J. S., Li, H., Vrzalova, A., et al. (2020). Targeting the pregnane X receptor using microbial metabolite mimicry.Embo Molecular Medicine, 12(4), ARTN e11621. https://doi.org/10.15252/emmm.201911621.
Zhang, X., Li, T., Liu, S., Xu, Y., Meng, M., Li, X., et al. (2020). beta-glucan from Lentinus edodes inhibits breast cancer progression via the Nur77/HIF-1alpha axis. Bioscience Reports, 40(12). 10.1042/BSR20201006.
Wang, D., Zhu, X., Tang, X., Li, H., Yizhen, X., & Chen, D. (2020). Auxiliary antitumor effects of fungal proteins from Hericium erinaceus by target on the gut microbiota. Journal of Food Science, 85(6), 1872–1890. https://doi.org/10.1111/1750-3841.15134
Sondergaard, T. E., Hansen, F. T., Purup, S., Nielsen, A. K., Bonefeld-Jorgensen, E. C., Giese, H., et al. (2011). Fusarin C acts like an estrogenic agonist and stimulates breast cancer cells in vitro. Toxicology Letters, 205(2), 116–121. https://doi.org/10.1016/j.toxlet.2011.05.1029
Meng, L., Feng, B., Tao, H., Yang, T., Meng, Y., Zhu, W., et al. (2011). A novel antioestrogen agent (3R,6R)-bassiatin inhibits cell proliferation and cell cycle progression by repressing cyclin D1 expression in 17beta-oestradiol-treated MCF-7 cells. Cell Biology International, 35(6), 599–605. https://doi.org/10.1042/CBI20100765
Simmons, L., Kaufmann, K., Garcia, R., Schwar, G., Huch, V., & Muller, R. (2011). Bendigoles D-F, bioactive sterols from the marine sponge-derived Actinomadura sp. SBMs009. Bioorganic & Medicinal Chemistry, 19(22), 6570–6575. https://doi.org/10.1016/j.bmc.2011.05.044.
Nepelska, M., de Wouters, T., Jacouton, E., Beguet-Crespel, F., Lapaque, N., Dore, J., et al. (2017). Commensal gut bacteria modulate phosphorylation-dependent PPARgamma transcriptional activity in human intestinal epithelial cells. Science and Reports, 7, 43199. https://doi.org/10.1038/srep43199
Aichinger, G., Beisl, J., & Marko, D. (2018). The hop polyphenols xanthohumol and 8-prenyl-naringenin antagonize the estrogenic effects of fusarium mycotoxins in human endometrial cancer cells. Frontiers in Nutrition, 5, 85. https://doi.org/10.3389/fnut.2018.00085
Zhao, J. C., Luan, Z. L., Liang, J. H., Cheng, Z. B., Sun, C. P., Wang, Y. L., et al. (2018). Drechmerin H, a novel 1(2), 2(18)-diseco indole diterpenoid from the fungus Drechmeria sp as a natural agonist of human pregnane X receptor. Bioorganic Chemistry, 79, 250–256. https://doi.org/10.1016/j.bioorg.2018.05.001
Kovacs, P., Csonka, T., Kovacs, T., Sari, Z., Ujlaki, G., Sipos, A., et al. (2019). Lithocholic acid, a metabolite of the microbiome, increases oxidative stress in breast cancer. Cancers, 11(9), ARTN 1255. https://doi.org/10.3390/cancers11091255.
Sari, Z., Miko, E., Kovacs, T., Janko, L., Csonka, T., Lente, G., et al. (2020). Indolepropionic acid, a metabolite of the microbiome, has cytostatic properties in breast cancer by activating AHR and PXR receptors and inducing oxidative stress. Cancers, 12(9), ARTN 2411. https://doi.org/10.3390/cancers12092411.
Zhao, Y., Zhao, C. X., Lu, J., Wu, J., Li, C. H., Hu, Z. Y., et al. (2019). Sesterterpene MHO7 suppresses breast cancer cells as a novel estrogen receptor degrader. Pharmacological Research, 146, 104294. https://doi.org/10.1016/j.phrs.2019.104294
Li, T., Hu, S. M., Pang, X. Y., Wang, J. F., Yin, J. Y., Li, F. H., et al. (2020). The marine-derived furanone reduces intracellular lipid accumulation in vitro by targeting LXRalpha and PPARalpha. Journal of Cellular and Molecular Medicine, 24(6), 3384–3398. https://doi.org/10.1111/jcmm.15012
Liang, Z., Gu, T., Wang, J., She, J., Ye, Y., Cao, W., et al. (2021). Chromene and chromone derivatives as liver X receptors modulators from a marine-derived Pestalotiopsis neglecta fungus. Bioorganic Chemistry, 112, 104927.
Lev, E. (2003). Traditional healing with animals (zootherapy): Medieval to present-day Levantine practice. Journal of Ethnopharmacology, 85(1), 107–118. https://doi.org/10.1016/s0378-8741(02)00377-x
Alves, R. R. N., Rosa, I. L., & Santana, G. G. (2007). The role of animal-derived remedies as complementary medicine in Brazil. BioScience, 57(11), 949–955. https://doi.org/10.1641/B571107
Quave, C. L., Lohani, U., Verde, A., Fajardo, J., Rivera, D., Obon, C., et al. (2010). A comparative assessment of zootherapeutic remedies from selected areas in Albania, Italy, Spain and Nepal. Journal of Ethnobiology, 30(1), 92–125. https://doi.org/10.2993/0278-0771-30.1.92
Dominguez-Martin, E. M., Tavares, J., Rijo, P., & Diaz-Lanza, A. M. (2020). Zoopharmacology: A way to discover new cancer treatments. Biomolecules, 10(6), https://doi.org/10.3390/biom10060817.
Jang, A., Jo, C., Kang, K. S., & Lee, M. (2008). Antimicrobial and human cancer cell cytotoxic effect of synthetic angiotensin-converting enzyme (ACE) inhibitory peptides. Food Chemistry, 107(1), 327–336. https://doi.org/10.1016/j.foodchem.2007.08.036
Yu, L., Yang, L., An, W., & Su, X. L. (2014). Anticancer bioactive peptide-3 inhibits human gastric cancer growth by suppressing gastric cancer stem cells. Journal of Cellular Biochemistry, 115(4), 697–711. https://doi.org/10.1002/jcb.24711
Su, L. Y., Xu, G. H., Shen, J., Tuo, Y., Zhang, X. G., Jia, S. Q., et al. (2010). Anticancer bioactive peptide suppresses human gastric cancer growth through modulation of apoptosis and the cell cycle. Oncology Reports, 23(1), 3–9. https://doi.org/10.3892/or_00000599
Ganjam, L. S., Thornton, W. H., Marshall, R. T., & Macdonald, R. S. (1997). Antiproliferative effects of yogurt fractions obtained by membrane dialysis on cultured mammalian intestinal cells. Journal of Dairy Science, 80(10), 2325–2329. https://doi.org/10.3168/jds.S0022-0302(97)76183-6
Wu, X., Chen, D., & Xie, G. R. (2006). Effects of Gekko sulfated polysaccharide on the proliferation and differentiation of hepatic cancer cell line. Cell Biology International, 30(8), 659–664. https://doi.org/10.1016/j.cellbi.2006.04.005
Ding, X.-L., Man, Y.-N., Hao, J., Zhu, C.-H., Liu, C., Yang, X., et al. (2016). The antitumor effect of Gekko sulfated glycopeptide by inhibiting bFGF-induced lymphangiogenesis. BioMed Research International, 2016, 7396392. https://doi.org/10.1155/2016/7396392
Calcabrini, C., Catanzaro, E., Bishayee, A., Turrini, E., & Fimognari, C. (2017). Marine sponge natural products with anticancer potential: An updated review. Marine Drugs, 15(10), 310.
He, S., Mao, X., Zhang, T., Guo, X., Ge, Y., Ma, C., et al. (2016). Separation and nanoencapsulation of antitumor peptides from Chinese three-striped box turtle (Cuora trifasciata). Journal of Microencapsulation, 33(4), 344–354. https://doi.org/10.1080/02652048.2016.1194904
El Ouar, I., Braicu, C., Naimi, D., Irimie, A., & Berindan-Neagoe, I. (2017). Effect of Helix aspersa extract on TNFα, NF-κB and some tumor suppressor genes in breast cancer cell line Hs578T. Pharmacognosy Magazine, 13(50), 281.
Jeyamogan, S., Khan, N. A., & Siddiqui, R. (2017). Animals living in polluted environments are a potential source of anti-tumor molecule(s). Cancer Chemotherapy and Pharmacology, 80(5), 919–924.
Wang, L. H., Dong, C., Li, X., Han, W. Y., & Su, X. L. (2017). Anticancer potential of bioactive peptides from animal sources (review). Oncology Reports, 38(2), 637–651. https://doi.org/10.3892/or.2017.5778
Yang, C., Li, Q., & Li, Y. (2014). Targeting nuclear receptors with marine natural products. Marine Drugs, 12(2), 601–635.
Ramesh, C., Tulasi, B. R., Raju, M., Thakur, N., & Dufossé, L. (2021). Marine natural products from tunicates and their associated microbes. Marine Drugs, 19(6), 308.
Waheed, M., Hussain, M. B., Javed, A., Mushtaq, Z., Hassan, S., Shariati, M. A., et al. (2019). Honey and cancer: A mechanistic review. Clinical Nutrition, 38(6), 2499–2503.
Arung, E. T., Ramadhan, R., Khairunnisa, B., Amen, Y., Matsumoto, M., Nagata, M., et al. (2021). Cytotoxicity effect of honey, bee pollen, and propolis from seven stingless bees in some cancer cell lines. Saudi Journal of Biological Sciences, 28(12), 7182–7189.
Ding, J., Chua, P.-J., Bay, B.-H., & Gopalakrishnakone, P. (2014). Scorpion venoms as a potential source of novel cancer therapeutic compounds. Experimental Biology and Medicine, 239(4), 387–393.
Sarfo-Poku, C., Eshun, O., & Lee, K. H. (2016). Medical application of scorpion venom to breast cancer: A mini-review. Toxicon, 122, 109–112.
Lee, N., Spears, M. E., Carlisle, A. E., & Kim, D. (2020). Endogenous toxic metabolites and implications in cancer therapy. Oncogene, 39(35), 5709–5720.
O’Flaherty, J. T., Rogers, L. C., Paumi, C. M., Hantgan, R. R., Thomas, L. R., Clay, C. E., et al. (2005). 5-Oxo-ETE analogs and the proliferation of cancer cells. Biochimica et Biophysica Acta, 1736(3), 228–236. https://doi.org/10.1016/j.bbalip.2005.08.009
Pham, J. V., Yilma, M. A., Feliz, A., Majid, M. T., Maffetone, N., Walker, J. R., et al. (2019). A review of the microbial production of bioactive natural products and biologics. Frontiers in Microbiology, 10, 1404.
Sharma, M., Tuaine, J., McLaren, B., Waters, D. L., Black, K., Jones, L. M., et al. (2016). Chemotherapy agents alter plasma lipids in breast cancer patients and show differential effects on lipid metabolism genes in liver cells. Plos One, 11(1), ARTN e0148049. https://doi.org/10.1371/journal.pone.0148049.
Pirouzpanah, S., Asemani, S., Shayanfar, A., Baradaran, B., & Montazeri, V. (2019). The effects of Berberis vulgaris consumption on plasma levels of IGF-1, IGFBPs, PPAR-gamma and the expression of angiogenic genes in women with benign breast disease: A randomized controlled clinical trial. BMC Complementary and Alternative Medicine, 19(1), 324. https://doi.org/10.1186/s12906-019-2715-1
Komatsu, Y., Yoshino, T., Yamazaki, K., Yuki, S., Machida, N., Sasaki, T., et al. (2014). Phase 1 study of efatutazone, a novel oral peroxisome proliferator-activated receptor gamma agonist, in combination with FOLFIRI as second-line therapy in patients with metastatic colorectal cancer. Investigational New Drugs, 32(3), 473–480. https://doi.org/10.1007/s10637-013-0056-3
Hamilton-Reeves, J. M., Rebello, S. A., Thomas, W., Slaton, J. W., & Kurzer, M. S. (2007). Isoflavone-rich soy protein isolate suppresses androgen receptor expression without altering estrogen receptor-beta expression or serum hormonal profiles in men at high risk of prostate cancer. Journal of Nutrition, 137(7), 1769–1775. https://doi.org/10.1093/jn/137.7.1769
Zhang, X., Wang, Q., Neil, B., & Chen, X. A. (2010). Effect of lycopene on androgen receptor and prostate-specific antigen velocity. Chinese Medical Journal, 123(16), 2231–2236. https://doi.org/10.3760/cma.j.issn.0366-6999.2010.16.014
Ide, H., Tokiwa, S., Sakamaki, K., Nishio, K., Isotani, S., Muto, S., et al. (2010). Combined inhibitory effects of soy isoflavones and curcumin on the production of prostate-specific antigen. Prostate, 70(10), 1127–1133. https://doi.org/10.1002/pros.21147
Kwan, E. M., Spain, L., Anton, A., Gan, C. L., Garrett, L., Chang, D., et al. (2022). Avelumab combined with stereotactic ablative body radiotherapy in metastatic castration-resistant prostate cancer: The phase 2 ICE-PAC clinical trial. European Urology, 81(3), 253–262.
Bailly, C. (2019). Irinotecan: 25 years of cancer treatment. Pharmacological Research, 148, 104398.
Kciuk, M., Marciniak, B., & Kontek, R. (2020). Irinotecan—Still an important player in cancer chemotherapy: A comprehensive overview. International Journal of Molecular Sciences, 21(14), 4919.
Noda, K., Nishiwaki, Y., Kawahara, M., Negoro, S., Sugiura, T., Yokoyama, A., et al. (2002). Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. New England Journal of Medicine, 346(2), 85–91.
Fuchs, C., Mitchell, E. P., & Hoff, P. M. (2006). Irinotecan in the treatment of colorectal cancer. Cancer Treatment Reviews, 32(7), 491–503.
Feldman, E., Kalaycio, M., Weiner, G., Frankel, S., Schulman, P., Schwartzberg, L., et al. (2003). Treatment of relapsed or refractory acute myeloid leukemia with humanized anti-CD33 monoclonal antibody HuM195. Leukemia, 17(2), 314–318.
Grillo-López, A. J., White, C. A., Varns, C., Shen, D., Wei, A., McClure, A., et al. Overview of the clinical development of rituximab: First monoclonal antibody approved for the treatment of lymphoma. In Seminars in Oncology, 1999 (Vol. 26, pp. 66–73, Vol. 5 Suppl 14)
Seiden, M., Burris, H., Matulonis, U., Hall, J., Armstrong, D., Speyer, J., et al. (2007). A phase II trial of EMD72000 (matuzumab), a humanized anti-EGFR monoclonal antibody, in patients with platinum-resistant ovarian and primary peritoneal malignancies. Gynecologic Oncology, 104(3), 727–731.
Smaletz, O., Ismael, G., Estevez-Diz, M. D. P., Nascimento, I. L., de Morais, A. L. G., Cunha-Junior, G. F., et al. (2021). Phase II consolidation trial with anti-Lewis-Y monoclonal antibody (hu3S193) in platinum-sensitive ovarian cancer after a second remission. International Journal of Gynecologic Cancer, 31(4), 62–568. https://doi.org/10.1136/ijgc-2020-002239
Chi, K. N., Gleave, M. E., Fazli, L., Goldenberg, S. L., So, A., Kollmannsberger, C., et al. (2012). A phase II pharmacodynamic study of preoperative figitumumab in patients with localized prostate cancer. Clinical Cancer Research, 18(12), 3407–3413. https://doi.org/10.1158/1078-0432.CCR-12-0482
Hor, S., Lee, S., Wong, C., Lim, Y., Lim, R., Wang, L., et al. (2008). PXR, CAR and HNF4α genotypes and their association with pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin in Asian patients. The Pharmacogenomics Journal, 8(2), 139–146.
Chew, S.-C., Lim, J., Singh, O., Chen, X., Tan, E.-H., Lee, E.-J., et al. (2014). Pharmacogenetic effects of regulatory nuclear receptors (PXR, CAR, RXRα and HNF4α) on docetaxel disposition in Chinese nasopharyngeal cancer patients. European Journal of Clinical Pharmacology, 70(2), 155–166.
Deeken, J. F., Cormier, T., Price, D. K., Sissung, T. M., Steinberg, S. M., Tran, K., et al. (2010). A pharmacogenetic study of docetaxel and thalidomide in patients with castration-resistant prostate cancer using the DMET genotyping platform. Pharmacogenomics Journal, 10(3), 191–199. https://doi.org/10.1038/tpj.2009.57
Funding
This work was supported by the BT/556/NE/U-Excel/2016 grant awarded to Ajaikumar B. Kunnumakkara by the Department of Biotechnology (DBT), Government of India. The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University (KKU) for funding this work through the Research Group Program under Grant Number: (R.G.P.2/133/43). Mangala Hegde received funding from Science and Engineering Board (SERB)-National Post-Doctoral Fellowship (NPDF) (PDF/2021/004053). Aviral Kumar acknowledge the Prime Minsiter’s Research Fellowship (PMRF) program, Ministry of Education (MoE), Govt. of India for providing fellwoship.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Hegde, M., Girisa, S., Naliyadhara, N. et al. Natural compounds targeting nuclear receptors for effective cancer therapy. Cancer Metastasis Rev 42, 765–822 (2023). https://doi.org/10.1007/s10555-022-10068-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10555-022-10068-w