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Reviews of Physiology, Biochemistry and Pharmacology, Vol. 171 pp 1–38Cite as

Curcumin as a MicroRNA Regulator in Cancer: A Review

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Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 171))

Abstract

Curcumin is a natural dietary polyphenol for which anti-tumor effects have been documented. Anti-inflammatory and antioxidant properties of curcumin, along with its immunomodulatory, proapoptotic, and antiangiogenic properties, are often referred to as the main mechanisms underlying the anti-tumor effects. At the molecular level, inhibition of NF-kB, Akt/PI3K, and MAPK pathways and enhancement of p53 are among the most important anticancer alterations induced by curcumin. Recent evidence has suggested that epigenetic alterations are also involved in the anti-tumor properties of curcumin. Among these curcumin-induced epigenetic alterations is modulation of the expression of several oncogenic and tumor suppressor microRNAs (miRNAs). Suppression of oncomiRs such as miR-21, miR-17-5p, miR-20a, and miR-27a and over-expression of miR-34 a/c and epithelial-mesenchymal transition-suppressor miRNAs are among the most important effects of curcumin on miRNA homeostasis. The present review will summarize the findings of in vitro and experimental studies on the impact of curcumin and its analogues on the expression of miRNAs involved in different stages of tumor initiation, growth, metastasis, and chemo-resistance.

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Abbreviations

5FUR:

5-Fluorouracil resistant

Bcl-2:

B cell lymphoma 2

CAM:

Chick chorioallantoic membrane

CDF:

Difluorinated-curcumin

ChIP:

Chromatin immuno precipitation

CR:

Chemo-resistant

CS:

Chemo-sensitive

CSC:

Cancer stem cells

EMT:

Epithelial-mesenchymal transition

ESR1:

Estrogen receptor 1

MDR1:

Multidrug resistance protein 1

OSCC:

Oral squamous-cell carcinoma

PCNA:

Proliferating cell nuclear antigen

PDCD4:

Programmed cell death protein 4

PRC:

Polycomb repressive complexes

PTEN:

Phosphatase and tensin homolog deleted on chromosome 10

Sp:

Specificity protein

WT1:

Wilm’s tumor 1

References

  • Adams BK, Ferstl EM, Davis MC, Herold M, Kurtkaya S, Camalier RF, Hollingshead MG, Kaur G, Sausville EA, Rickles FR (2004) Synthesis and biological evaluation of novel curcumin analogs as anti-cancer and anti-angiogenesis agents. Bioorg Med Chem 12:3871–3883

    Article  CAS  PubMed  Google Scholar 

  • Aggarwal BB, Shishodia S (2006) Molecular targets of dietary agents for prevention and therapy of cancer. Biochem Pharmacol 71:1397–1421

    Article  CAS  PubMed  Google Scholar 

  • Aggarwal S, Takada Y, Singh S, Myers JN, Aggarwal BB (2004) Inhibition of growth and survival of human head and neck squamous cell carcinoma cells by curcumin via modulation of nuclear factor‐kB signaling. Int J Cancer 111:679–692

    Article  CAS  PubMed  Google Scholar 

  • Ahmad A, Sayed A, Ginnebaugh KR, Sharma V, Suri A, Saraph A, Padhye S, Sarkar FH (2015) Molecular docking and inhibition of matrix metalloproteinase-2 by novel difluorinatedbenzylidene curcumin analog. Am J Transl Res 7:298–308

    CAS  PubMed  PubMed Central  Google Scholar 

  • Akram M, Shahab-Uddin AA, Usmanghani K, Hannan A, Mohiuddin E, Asif M (2010) Curcuma longa and curcumin: a review article. Rom J Biol Plant Biol 55:65–70

    Google Scholar 

  • Al-Ansari MM, Aboussekhra A (2015) miR-146b-5p mediates p16-dependent repression of IL-6 and suppresses paracrine procarcinogenic effects of breast stromal fibroblasts. Oncotarget 6:30006–30016

    PubMed  PubMed Central  Google Scholar 

  • Ali S, Ahmad A, Banerjee S, Padhye S, Dominiak K, Schaffert JM, Wang Z, Philip PA, Sarkar FH (2010) Gemcitabine sensitivity can be induced in pancreatic cancer cells through modulation of miR-200 and miR-21 expression by curcumin or its analogue CDF. Cancer Res 70:3606–3617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ali S, Ahmad A, Aboukameel A, Bao B, Padhye S, Philip PA, Sarkar FH (2012) Increased Ras GTPase activity is regulated by miRNAs that can be attenuated by CDF treatment in pancreatic cancer cells. Cancer Lett 319:173–181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ambros V (2003) MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell 113:673–676

    Article  CAS  PubMed  Google Scholar 

  • Arafa HM (2005) Curcumin attenuates diet-induced hypercholesterolemia in rats. Med Sci Monit 11:BR228–BR234

    Google Scholar 

  • Asai A, Miyazawa T (2001) Dietary curcuminoids prevent high-fat diet-induced lipid accumulation in rat liver and epididymal adipose tissue. J Nutr 131:2932–2935

    CAS  PubMed  Google Scholar 

  • Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S, Allgayer H (2008) MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 27:2128–2136

    Article  CAS  PubMed  Google Scholar 

  • Balasubramanyam K, Varier RA, Altaf M, Swaminathan V, Siddappa NB, Ranga U, Kundu TK (2004) Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription. J Biol Chem 279:51163–51171

    Article  CAS  PubMed  Google Scholar 

  • Bao B, Ali S, Kong D, Sarkar SH, Wang Z, Banerjee S, Aboukameel A, Padhye S, Philip PA, Sarkar FH (2011) Anti-tumor activity of a novel compound-CDF is mediated by regulating miR-21, miR-200, and PTEN in pancreatic cancer. PLoS One 6, e17850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bao B, Ali S, Banerjee S, Wang Z, Logna F, Azmi AS, Kong D, Ahmad A, Li Y, Padhye S (2012) Curcumin analogue CDF inhibits pancreatic tumor growth by switching on suppressor microRNAs and attenuating EZH2 expression. Cancer Res 72:335–345

    Article  CAS  PubMed  Google Scholar 

  • Brighenti M (2015) MicroRNA and MET in lung cancer. Ann Transl Med 3:68

    PubMed  PubMed Central  Google Scholar 

  • Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, Feldmann G, Yamakuchi M, Ferlito M, Lowenstein CJ, Arking DE, Beer MA, Maitra A, Mendell JT (2007) Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell 26:745–752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen A, Xu J, Johnson A (2006) Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1. Oncogene 25:278–287

    PubMed  Google Scholar 

  • Chen K, An Y, Tie L, Pan Y, Li X (2015) Curcumin protects neurons from glutamate-induced excitotoxicity by membrane anchored AKAP79-PKA interaction network. Evid Based Complement Alternat Med 2015:706207

    PubMed  PubMed Central  Google Scholar 

  • Choudhuri T, Pal S, Das T, Sa G (2005) Curcumin selectively induces apoptosis in deregulated cyclin D1-expressed cells at G2 phase of cell cycle in a p53-dependent manner. J Biol Chem 280:20059–20068

    Article  CAS  PubMed  Google Scholar 

  • Collett GP, Campbell FC (2004) Curcumin induces c-jun N-terminal kinase-dependent apoptosis in HCT116 human colon cancer cells. Carcinogenesis 25:2183–2189

    Article  CAS  PubMed  Google Scholar 

  • Corney DC, Flesken-Nikitin A, Godwin AK, Wang W, Nikitin AY (2007) MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res 67:8433–8438

    Article  CAS  PubMed  Google Scholar 

  • Dahmke IN, Backes C, Rudzitis-Auth J, Laschke MW, Leidinger P, Menger MD, Meese E, Mahlknecht U (2013) Curcumin intake affects miRNA signature in murine melanoma with mmu-miR-205-5p most significantly altered. PLoS One 8, e81122

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Das PM, Singal R (2004) DNA methylation and cancer. J Clin Oncol 22:4632–4642

    Article  CAS  PubMed  Google Scholar 

  • Esmaily H, Sahebkar A, Iranshahi M, Ganjali S, Mohammadi A, Ferns G, Ghayour-Mobarhan M (2015) An investigation of the effects of curcumin on anxiety and depression in obese individuals: a randomized controlled trial. Chin J Integr Med 21:332–338

    Article  CAS  PubMed  Google Scholar 

  • Fan C, Wo X, Qian Y, Yin J, Gao L (2006) Effect of curcumin on the expression of LDL receptor in mouse macrophages. J Ethnopharmacol 105:251–254

    Article  CAS  PubMed  Google Scholar 

  • Gandhy SU, Kim K, Larsen L, Rosengren RJ, Safe S (2012) Curcumin and synthetic analogs induce reactive oxygen species and decreases specificity protein (Sp) transcription factors by targeting microRNAs. BMC Cancer 12:564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ganjali S, Sahebkar A, Mahdipour E, Jamialahmadi K, Torabi S, Akhlaghi S, Ferns G, Parizadeh SMR, Ghayour-Mobarhan M (2014) Investigation of the effects of curcumin on serum cytokines in obese individuals: a randomized controlled trial. ScientificWorldJournal 2014:898361

    Google Scholar 

  • Gao SM, Yang JJ, Chen CQ, Chen JJ, Ye LP, Wang LY, Wu JB, Xing CY, Yu K (2012) Pure curcumin decreases the expression of WT1 by upregulation of miR-15a and miR-16-1 in leukemic cells. J Exp Clin Cancer Res 31:27

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gao W, Chan JY-W, Wong T-S (2014) Curcumin exerts inhibitory effects on undifferentiated nasopharyngeal carcinoma by inhibiting the expression of miR-125a-5p. Clin Sci 127:571–579

    Article  CAS  PubMed  Google Scholar 

  • Gleissner CA, Erbel C, Haeussler J, Akhavanpoor M, Domschke G, Linden F, Doesch AO, Conradson G, Buss SJ, Hofmann NP, Gitsioudis G, Katus HA, Korosoglou G (2014) Low levels of natural IgM antibodies against phosphorylcholine are independently associated with vascular remodeling in patients with coronary artery disease. Clin Res Cardiol 104:13–22

    Article  PubMed  CAS  Google Scholar 

  • Grunstein M (1997) Histone acetylation in chromatin structure and transcription. Nature 389:349–352

    Article  CAS  PubMed  Google Scholar 

  • Guo J, Li W, Shi H, Xie X, Li L, Tang H, Wu M, Kong Y, Yang L, Gao J (2013) Synergistic effects of curcumin with emodin against the proliferation and invasion of breast cancer cells through upregulation of miR-34a. Mol Cell Biochem 382:103–111

    Article  CAS  PubMed  Google Scholar 

  • Guo H, Xu Y, Fu Q (2015) Curcumin inhibits growth of prostate carcinoma via miR-208-mediated CDKN1A activation. Tumour Biol 36(11):8511–8517. doi:10.1007/s13277-015-3592-y

    Article  CAS  PubMed  Google Scholar 

  • Gupta SC, Kim JH, Prasad S, Aggarwal BB (2010) Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals. Cancer Metastasis Rev 29:405–434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hammond SM (2015) An overview of microRNAs. Adv Drug Deliv Rev 87:3–14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang A, Wang X, Shan X, Li Y, Wang P, Jiang P, Feng Q (2015) Curcumin reactivates silenced tumor suppressor gene RARbeta by reducing DNA methylation. Phytother Res 29:1237–1245

    Article  CAS  PubMed  Google Scholar 

  • Jin H, Qiao F, Wang Y, Xu Y, Shang Y (2015) Curcumin inhibits cell proliferation and induces apoptosis of human non-small cell lung cancer cells through the upregulation of miR-192-5p and suppression of PI3K/Akt signaling pathway. Oncol Rep 34:2782–2789

    PubMed  Google Scholar 

  • Jordan W, Drew C (1996) Curcumin—a natural herb with anti-HIV activity. J Natl Med Assoc 88:333

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jurenka JS (2009) Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev 14:277

    Google Scholar 

  • Kanwar SS, Yu Y, Nautiyal J, Patel BB, Padhye S, Sarkar FH, Majumdar AP (2011) Difluorinated-curcumin (CDF): a novel curcumin analog is a potent inhibitor of colon cancer stem-like cells. Pharm Res 28:827–838

    Article  CAS  PubMed  Google Scholar 

  • Kim M-k, G-j C, Lee H-s (2003) Fungicidal property of Curcuma longa L. rhizome-derived curcumin against phytopathogenic fungi in a greenhouse. J Agric Food Chem 51:1578–1581

    Article  CAS  PubMed  Google Scholar 

  • Kronski E, Fiori ME, Barbieri O, Astigiano S, Mirisola V, Killian PH, Bruno A, Pagani A, Rovera F, Pfeffer U (2014) miR181b is induced by the chemopreventive polyphenol curcumin and inhibits breast cancer metastasis via down-regulation of the inflammatory cytokines CXCL1 and-2. Mol Oncol 8:581–595

    Article  CAS  PubMed  Google Scholar 

  • Kumar K, Rai AK (2012) Proniosomal formulation of curcumin having anti-inflammatory and anti-arthritic activity in different experimental animal models. Pharmazie 67:852–857

    CAS  PubMed  Google Scholar 

  • Kuncha M, Naidu VG, Sahu BD, Gadepalli SG, Sistla R (2014) Curcumin potentiates the anti-arthritic effect of prednisolone in Freund’s complete adjuvant-induced arthritic rats. J Pharm Pharmacol 66:133–144

    Article  CAS  PubMed  Google Scholar 

  • Kurzrock R, Li L (2005) Liposome-encapsulated curcumin: in vitro and in vivo effects on proliferation, apoptosis, signaling, and angiogenesis. In: ASCO annual meeting proceedings, p 4091

    Google Scholar 

  • Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, Kim VN (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23:4051–4060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee SJ, Krauthauser C, Maduskuie V, Fawcett PT, Olson JM, Rajasekaran SA (2011) Curcumin-induced HDAC inhibition and attenuation of medulloblastoma growth in vitro and in vivo. BMC Cancer 11:144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li L, Ahmed B, Mehta K, Kurzrock R (2007) Liposomal curcumin with and without oxaliplatin: effects on cell growth, apoptosis, and angiogenesis in colorectal cancer. Mol Cancer Ther 6:1276–1282

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Kong D, Wang Z, Sarkar FH (2010) Regulation of microRNAs by natural agents: an emerging field in chemoprevention and chemotherapy research. Pharm Res 27:1027–1041

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li X, Xie W, Xie C, Huang C, Zhu J, Liang Z, Deng F, Zhu M, Zhu W, Wu R (2014) Curcumin modulates miR‐19/PTEN/AKT/p53 axis to suppress bisphenol A‐induced MCF‐7 breast cancer cell proliferation. Phytother Res 28:1553–1560

    Article  CAS  PubMed  Google Scholar 

  • Liang HH, Wei PL, Hung CS, Wu CT, Wang W, Huang MT, Chang YJ (2013) MicroRNA-200a/b influenced the therapeutic effects of curcumin in hepatocellular carcinoma (HCC) cells. Tumour Biol 34:3209–3218

    Article  CAS  PubMed  Google Scholar 

  • Lu W-C, Kao S-Y, Yang C-C, Tu H-F, Wu C-H, Chang K-W, Lin S-C (2014) EGF up-regulates miR-31 through the C/EBPβ signal cascade in oral carcinoma. PLoS One 9, e108049

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ma J, Fang B, Zeng F, Pang H, Zhang J, Shi Y, Wu X, Cheng L, Ma C, Xia J (2014) Curcumin inhibits cell growth and invasion through up-regulation of miR-7 in pancreatic cancer cells. Toxicol Lett 231:82–91

    Article  CAS  PubMed  Google Scholar 

  • Mahady G, Pendland S, Yun G, Lu Z (2001) Turmeric (Curcuma longa) and curcumin inhibit the growth of Helicobacter pylori, a group 1 carcinogen. Anticancer Res 22:4179–4181

    Google Scholar 

  • Mani S, Herceg Z (2010) DNA demethylating agents and epigenetic therapy of cancer. Adv Genet 70:327–340

    CAS  PubMed  Google Scholar 

  • Mao L, Hruban RH, Boyle JO, Tockman M, Sidransky D (1994) Detection of oncogene mutations in sputum precedes diagnosis of lung cancer. Cancer Res 54:1634–1637

    CAS  PubMed  Google Scholar 

  • Mirgani MT, Isacchi B, Sadeghizadeh M, Marra F, Bilia AR, Mowla SJ, Najafi F, Babaei E (2014) Dendrosomal curcumin nanoformulation downregulates pluripotency genes via miR-145 activation in U87MG glioblastoma cells. Int J Nanomedicine 9:403

    Google Scholar 

  • Mirzaei H, Naseri G, Rezaee R, Mohammadi M, Banikazemi Z, Reza Mirzaei H, Salehi H, Peyvandi M, Pawelek JM, Sahebkar A (2016) Curcumin: a new candidate for melanoma therapy? Int J Cancer. doi:10.1002/ijc.30224

    PubMed  Google Scholar 

  • Mohammadi A, Sahebkar A, Iranshahi M, Amini M, Khojasteh R, Ghayour-Mobarhan M, Ferns GA (2013) Effects of supplementation with curcuminoids on dyslipidemia in obese patients: a randomized crossover trial. Phytother Res 27:374–379

    Article  CAS  PubMed  Google Scholar 

  • Momtazi AA, Sahebkar A (2016) Difluorinated curcumin: a promising curcumin analogue with improved anti-tumor activity and pharmacokinetic profile. Curr Pharm Des. doi:10.2174/1381612822666160527113501

    PubMed  Google Scholar 

  • Momtazi AA, Derosa G, Maffioli P, Banach M, Sahebkar A (2016) Role of microRNAs in the therapeutic effects of curcumin in non-cancer diseases. Mol Diagn Ther. doi:10.1007/s40291-016-0202-7

    PubMed  Google Scholar 

  • Mudduluru G, George-William J, Muppala S, Asangani I, Kumarswamy R, Nelson L, Allgayer H (2011) Curcumin regulates miR-21 expression and inhibits invasion and metastasis in colorectal cancer. Biosci Rep 31:185–197

    Article  CAS  PubMed  Google Scholar 

  • NCI D (1996) Clinical development plan: curcumin. J Cell Biochem Suppl 26:72–85

    Google Scholar 

  • Negi P, Jayaprakasha G, Jagan Mohan Rao L, Sakariah K (1999) Antibacterial activity of turmeric oil: a byproduct from curcumin manufacture. J Agric Food Chem 47:4297–4300

    Article  CAS  PubMed  Google Scholar 

  • Nishiyama T, Mae T, Kishida H, Tsukagawa M, Mimaki Y, Kuroda M, Sashida Y, Takahashi K, Kawada T, Nakagawa K (2005) Curcuminoids and sesquiterpenoids in turmeric (Curcuma longa L.) suppress an increase in blood glucose level in type 2 diabetic KK-Ay mice. J Agric Food Chem 53:959–963

    Article  CAS  PubMed  Google Scholar 

  • Noratto GD, Jutooru I, Safe S, Angel-Morales G, Mertens-Talcott SU (2013) The drug resistance suppression induced by curcuminoids in colon cancer SW‐480 cells is mediated by reactive oxygen species‐induced disruption of the microRNA‐27a‐ZBTB10‐Sp axis. Mol Nutr Food Res 57:1638–1648

    Article  CAS  PubMed  Google Scholar 

  • Panahi Y, Sahebkar A, Amiri M, Davoudi SM, Beiraghdar F, Hoseininejad SL, Kolivand M (2012a) Improvement of sulphur mustard-induced chronic pruritus, quality of life and antioxidant status by curcumin: results of a randomised, double-blind, placebo-controlled trial. Br J Nutr 108:1272–1279

    Article  CAS  PubMed  Google Scholar 

  • Panahi Y, Sahebkar A, Parvin S, Saadat A (2012b) A randomized controlled trial on the anti-inflammatory effects of curcumin in patients with chronic sulphur mustard-induced cutaneous complications. Ann Clin Biochem 49:580–588

    Article  CAS  PubMed  Google Scholar 

  • Panahi Y, Rahimnia AR, Sharafi M, Alishiri G, Saburi A, Sahebkar A (2014a) Curcuminoid treatment for knee osteoarthritis: a randomized double-blind placebo-controlled trial. Phytother Res 28:1625–1631

    Article  CAS  PubMed  Google Scholar 

  • Panahi Y, Saadat A, Beiraghdar F, Sahebkar A (2014b) Adjuvant therapy with bioavailability-boosted curcuminoids suppresses systemic inflammation and improves quality of life in patients with solid tumors: a randomized double-blind placebo-controlled trial. Phytother Res 28:1461–1467

    Article  CAS  PubMed  Google Scholar 

  • Panahi Y, Badeli R, Karami GR, Sahebkar A (2015) Investigation of the efficacy of adjunctive therapy with bioavailability-boosted curcuminoids in major depressive disorder. Phytother Res 29:17–21

    Article  CAS  PubMed  Google Scholar 

  • Panahi Y, Alishiri GH, Parvin S, Sahebkar A (2016) Mitigation of systemic oxidative stress by curcuminoids in osteoarthritis: results of a randomized controlled trial. J Diet Suppl 13:209–220

    Article  CAS  PubMed  Google Scholar 

  • Panahi Y, Kianpour P, Mohtashami R, Jafari R, Simental-Mendía LE, Sahebkar A (2016) Curcumin lowers serum lipids and uric acid in subjects with non-alcoholic fatty liver disease: a randomized controlled trial. J Cardiovasc Pharmacol. doi:10.1097/FJC.0000000000000406

    PubMed  Google Scholar 

  • Rahmani S, Asgary S, Askari G, Keshvari M, Hatamipour M, Feizi A, Sahebkar A (2016) Treatment of non-alcoholic fatty liver disease with curcumin: a randomized placebo-controlled trial. Phytother Res. doi:10.1002/ptr.5659

    PubMed  Google Scholar 

  • Reddy RC, Vatsala PG, Keshamouni VG, Padmanaban G, Rangarajan PN (2005) Curcumin for malaria therapy. Biochem Biophys Res Commun 326:472–474

    Article  CAS  PubMed  Google Scholar 

  • Reid JM, Buhrow SA, Gilbert JA, Jia L, Shoji M, Snyder JP, Ames MM (2014) Mouse pharmacokinetics and metabolism of the curcumin analog, 4-piperidinone, 3,5-bis [(2-fluorophenyl) methylene]-acetate (3E, 5E)(EF-24; NSC 716993). Cancer Chemother Pharmacol 73:1137–1146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roy S, Levi E, Majumdar A, Sarkar FH (2012) Expression of miR-34 is lost in colon cancer which can be re-expressed by a novel agent CDF. J Hematol Oncol 5:58

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roy S, Yu Y, Padhye SB, Sarkar FH, Majumdar AP (2013) Difluorinated-curcumin (CDF) restores PTEN expression in colon cancer cells by down-regulating miR-21. PLoS One 8, e68543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sahebkar A (2010) Molecular mechanisms for curcumin benefits against ischemic injury. Fertil Steril 94:e75–e76; author reply e77

    Google Scholar 

  • Sahebkar A (2013) Why it is necessary to translate curcumin into clinical practice for the prevention and treatment of metabolic syndrome? Biofactors 39:197–208

    Article  CAS  PubMed  Google Scholar 

  • Sahebkar A (2014) Are curcuminoids effective C-reactive protein-lowering agents in clinical practice? Evidence from a meta-analysis. Phytother Res 28:633–642

    Article  CAS  PubMed  Google Scholar 

  • Sahebkar A (2016) Autophagic activation: a key piece of the puzzle for the curcumin-associated cognitive enhancement? J Psychopharmacol 30:93–94

    Article  CAS  PubMed  Google Scholar 

  • Sahebkar A, Henrotin Y (2015) Analgesic efficacy and safety of curcuminoids in clinical practice: a systematic review and meta-analysis of randomized controlled trials. Pain Med

    Google Scholar 

  • Sahebkar A, Mohammadi A, Atabati A, Rahiman S, Tavallaie S, Iranshahi M, Akhlaghi S, Ferns GA, Ghayour-Mobarhan M (2013) Curcuminoids modulate pro‐oxidant–antioxidant balance but not the immune response to heat shock protein 27 and oxidized LDL in obese individuals. Phytother Res 27:1883–1888

    Article  CAS  PubMed  Google Scholar 

  • Sahebkar A, Chew GT, Watts GF (2014) Recent advances in pharmacotherapy for hypertriglyceridemia. Prog Lipid Res 56:47–66

    Article  CAS  PubMed  Google Scholar 

  • Sahebkar A, Serban MC, Ursoniu S, Banach M (2015) Effect of curcuminoids on oxidative stress: a systematic review and meta-analysis of randomized controlled trials. J Funct Foods 18:898–909

    Article  CAS  Google Scholar 

  • Sahebkar A, Cicero AF, Simental-Mendia LE, Aggarwal BB, Gupta SC (2016) Curcumin downregulates human tumor necrosis factor-alpha levels: a systematic review and meta-analysis of randomized controlled trials. Pharmacol Res 107:234–242

    Article  CAS  PubMed  Google Scholar 

  • Saini S, Arora S, Majid S, Shahryari V, Chen Y, Deng G, Yamamura S, Ueno K, Dahiya R (2011) Curcumin modulates microRNA-203-mediated regulation of the Src-Akt axis in bladder cancer. Cancer Prev Res (Phila) 4:1698–1709

    Article  CAS  PubMed Central  Google Scholar 

  • Sankar P, Telang AG, Suresh S, Kesavan M, Kannan K, Kalaivanan R, Sarkar SN (2013) Immunomodulatory effects of nanocurcumin in arsenic-exposed rats. Int Immunopharmacol 17:65–70

    Article  CAS  PubMed  Google Scholar 

  • Sarkar S, Dubaybo H, Ali S, Goncalves P, Kollepara SL, Sethi S, Philip PA, Li Y (2013) Down-regulation of miR-221 inhibits proliferation of pancreatic cancer cells through up-regulation of PTEN, p27(kip1), p57(kip2), and PUMA. Am J Cancer Res 3:465–477

    PubMed  PubMed Central  Google Scholar 

  • Sawan C, Vaissière T, Murr R, Herceg Z (2008) Epigenetic drivers and genetic passengers on the road to cancer. Mutat Res 642:1–13

    Article  CAS  PubMed  Google Scholar 

  • Seyedzadeh MH, Safari Z, Zare A, Gholizadeh Navashenaq J, Razavi SA, Kardar GA, Khorramizadeh MR (2014) Study of curcumin immunomodulatory effects on reactive astrocyte cell function. Int Immunopharmacol 22:230–235

    Article  CAS  PubMed  Google Scholar 

  • Shakeri A, Sahebkar A (2016) Optimized curcumin formulations for the treatment of Alzheimer’s disease: a patent evaluation. J Neurosci Res 94:111–113

    Article  CAS  PubMed  Google Scholar 

  • Shankar S, Srivastava RK (2007) Involvement of Bcl-2 family members, phosphatidylinositol 3′-kinase/AKT and mitochondrial p53 in curcumin (diferulolylmethane)-induced apoptosis in prostate cancer. Int J Oncol 30:905–918

    CAS  PubMed  Google Scholar 

  • Sharma O (1976) Antioxidant activity of curcumin and related compounds. Biochem Pharmacol 25:1811–1812

    Article  CAS  PubMed  Google Scholar 

  • Sharma S, Kulkarni SK, Chopra K (2006) Curcumin, the active principle of turmeric (Curcuma longa), ameliorates diabetic nephropathy in rats. Clin Exp Pharmacol Physiol 33:940–945

    Article  CAS  PubMed  Google Scholar 

  • Shen LL, Jiang ML, Liu SS, Cai MC, Hong ZQ, Lin LQ, Xing YY, Chen GL, Pan R, Yang LJ, Xu Y, Dong J (2015) Curcumin improves synaptic plasticity impairment induced by HIV-1gp120 V3 loop. Neural Regen Res 10:925–931

    Article  PubMed  PubMed Central  Google Scholar 

  • Shu L, Khor TO, Lee J-H, Boyanapalli SS, Huang Y, Wu T-Y, Saw CL-L, Cheung K-L, Kong A-NT (2011) Epigenetic CpG demethylation of the promoter and reactivation of the expression of Neurog1 by curcumin in prostate LNCaP cells. AAPS J 13:606–614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sidhu GS, Singh AK, Thaloor D, Banaudha KK, Patnaik GK, Srimal RC, Maheshwari RK (1998) Enhancement of wound healing by curcumin in animals. Wound Repair Regen 6:167–177

    Article  CAS  PubMed  Google Scholar 

  • Sreenivasan S, Thirumalai K, Danda R, Krishnakumar S (2012) Effect of curcumin on miRNA expression in human Y79 retinoblastoma cells. Curr Eye Res 37:421–428

    Article  CAS  PubMed  Google Scholar 

  • Steger DJ, Workman JL (1996) Remodeling chromatin structures for transcription: what happens to the histones? Bioessays 18:875–884

    Article  CAS  PubMed  Google Scholar 

  • Strimpakos AS, Sharma RA (2008) Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials. Antioxid Redox Signal 10:511–546

    Article  CAS  PubMed  Google Scholar 

  • Subramaniam D, Ponnurangam S, Ramamoorthy P, Standing D, Battafarano RJ, Anant S, Sharma P (2012) Curcumin induces cell death in esophageal cancer cells through modulating Notch signaling. PLoS One 7, e30590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun Y (2006) p53 and its downstream proteins as molecular targets of cancer. Mol Carcinog 45:409–415

    Article  CAS  PubMed  Google Scholar 

  • Sun M, Estrov Z, Ji Y, Coombes KR, Harris DH, Kurzrock R (2008) Curcumin (diferuloylmethane) alters the expression profiles of microRNAs in human pancreatic cancer cells. Mol Cancer Ther 7:464–473

    Article  CAS  PubMed  Google Scholar 

  • Tang N, Zhang J, Du Y (2010) [Curcumin promoted the apoptosis of cisplain-resistant human lung carcinoma cells A549/DDP through down-regulating miR-186*]. Zhongguo Fei Ai Za Zhi 13:301–306

    Google Scholar 

  • Taverna S, Giallombardo M, Pucci M, Flugy A, Manno M, Raccosta S, Rolfo C, De Leo G, Alessandro R (2015) Curcumin inhibits in vitro and in vivo chronic myelogenous leukemia cells growth: a possible role for exosomal disposal of miR-21. Oncotarget 6:21918–21933

    Article  PubMed  PubMed Central  Google Scholar 

  • Teiten M-H, Gaigneaux A, Chateauvieux S, Billing AM, Planchon S, Fack F, Renaut J, Mack F, Muller CP, Dicato M (2012) Identification of differentially expressed proteins in curcumin-treated prostate cancer cell lines. OMICS 16:289–300

    Article  CAS  PubMed  Google Scholar 

  • Teiten MH, Dicato M, Diederich M (2013) Curcumin as a regulator of epigenetic events. Mol Nutr Food Res 57:1619–1629

    Article  CAS  PubMed  Google Scholar 

  • Toden S, Okugawa Y, Jascur T, Wodarz D, Komarova NL, Buhrmann C, Shakibaei M, Boland CR, Goel A (2015) Curcumin mediates chemosensitization to 5-fluorouracil through miRNA-induced suppression of epithelial-to-mesenchymal transition in chemoresistant colorectal cancer. Carcinogenesis 36:355–367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ueno K, Hirata H, Shahryari V, Deng G, Tanaka Y, Tabatabai ZL, Hinoda Y, Dahiya R (2013) microRNA-183 is an oncogene targeting Dkk-3 and SMAD4 in prostate cancer. Br J Cancer 108:1659–1667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Um MY, Hwang KH, Choi WH, Ahn J, Jung CH, Ha TY (2014) Curcumin attenuates adhesion molecules and matrix metalloproteinase expression in hypercholesterolemic rabbits. Nutr Res 34:886–893

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Lee CG (2009) MicroRNA and cancer-focus on apoptosis. J Cell Mol Med 13:12–23

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Li J, Zhuge L, Su D, Yang M, Tao S (2014) Comparison between the efficacies of curcumin and puerarin in C57BL/6 mice with steatohepatitis induced by a methionine- and choline-deficient diet. Exp Ther Med 7:663–668

    CAS  PubMed  Google Scholar 

  • Wang BF, Cui ZW, Zhong ZH, Sun YH, Sun QF, Yang GY, Bian LG (2015) Curcumin attenuates brain edema in mice with intracerebral hemorrhage through inhibition of AQP4 and AQP9 expression. Acta Pharmacol Sin 36:939–948

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J, Xie H, Gao F, Zhao T, Yang H, Kang B (2016) Curcumin induces apoptosis in p53-null Hep3B cells through a TAp73/DNp73-dependent pathway. Tumour Biol 37:4203–4212

    Article  CAS  PubMed  Google Scholar 

  • Williams RJ, Spencer JP (2012) Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease. Free Radic Biol Med 52:35–45

    Article  CAS  PubMed  Google Scholar 

  • Winter J, Jung S, Keller S, Gregory RI, Diederichs S (2009) Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 11:228–234

    Article  CAS  PubMed  Google Scholar 

  • Xiao C, Wang L, Zhu L, Zhang C, Zhou J (2014) Curcumin inhibits oral squamous cell carcinoma SCC-9 cells proliferation by regulating miR-9 expression. Biochem Biophys Res Commun 454:576–580

    Article  CAS  PubMed  Google Scholar 

  • Yallapu MM, Khan S, Maher DM, Ebeling MC, Sundram V, Chauhan N, Ganju A, Balakrishna S, Gupta BK, Zafar N (2014) Anti-cancer activity of curcumin loaded nanoparticles in prostate cancer. Biomaterials 35:8635–8648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang J, Cao Y, Sun J, Zhang Y (2010) Curcumin reduces the expression of Bcl-2 by upregulating miR-15a and miR-16 in MCF-7 cells. Med Oncol 27:1114–1118

    Article  CAS  PubMed  Google Scholar 

  • Yang CH, Yue J, Sims M, Pfeffer LM (2013) The curcumin analog EF24 targets NF-kappaB and miRNA-21, and has potent anticancer activity in vitro and in vivo. PLoS One 8, e71130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Y, Wu X, Wei Z, Dou Y, Zhao D, Wang T, Bian D, Tong B, Xia Y, Xia Y, Dai Y (2015) Oral curcumin has anti-arthritic efficacy through somatostatin generation via cAMP/PKA and Ca(2+)/CaMKII signaling pathways in the small intestine. Pharmacol Res 95–96:71–81

    Article  PubMed  CAS  Google Scholar 

  • Ye M, Zhang J, Miao Q, Yao L (2015) Curcumin promotes apoptosis by activating the p53-miR-192-5p/215-XIAP pathway in non-small cell lung cancer. Cancer Lett 357:196–205

    Article  CAS  PubMed  Google Scholar 

  • Zamani M, Sadeghizadeh M, Behmanesh M, Najafi F (2015) Dendrosomal curcumin increases expression of the long non-coding RNA gene MEG3 via up-regulation of epi-miRs in hepatocellular cancer. Phytomedicine 22:961–967

    Article  CAS  PubMed  Google Scholar 

  • Zhang W, Bai W (2014) MiR-21 suppresses the anticancer activities of curcumin by targeting PTEN gene in human non-small cell lung cancer A549 cells. Clin Transl Oncol 16:708–713

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Du Y, Wu C, Ren X, Ti X, Shi J, Zhao F, Yin H (2010a) Curcumin promotes apoptosis in human lung adenocarcinoma cells through miR-186* signaling pathway. Oncol Rep 24:1217–1223

    CAS  PubMed  Google Scholar 

  • Zhang J, Zhang T, Ti X, Shi J, Wu C, Ren X, Yin H (2010b) Curcumin promotes apoptosis in A549/DDP multidrug-resistant human lung adenocarcinoma cells through an miRNA signaling pathway. Biochem Biophys Res Commun 399:1–6

    Article  CAS  PubMed  Google Scholar 

  • Zhang P, Bai H, Liu G, Wang H, Chen F, Zhang B, Zeng P, Wu C, Peng C, Huang C (2015) MicroRNA-33b, upregulated by EF24, a curcumin analog, suppresses the epithelial-to-mesenchymal transition (EMT) and migratory potential of melanoma cells by targeting HMGA2. Toxicol Lett 234:151–161

    Article  CAS  PubMed  Google Scholar 

  • Zhao S-F, Zhang X, Zhang X-J, Shi X-Q, Yu Z-J, Kan Q-C (2014) Induction of microRNA-9 mediates cytotoxicity of curcumin against SKOV3 ovarian cancer cells. Asian Pac J Cancer Prev 15:3363–3368

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Student Research Committee, Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Amir Abbas Momtazi

  2. Nanotechnology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Amir Abbas Momtazi

  3. National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran

    Fahimeh Shahabipour

  4. Neurogenic Inflammation Research Center, Department of Medical Biotechnology, Mashhad University of Medical Sciences, Mashhad, Iran

    Sepideh Khatibi

  5. Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA

    Thomas P. Johnston

  6. Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Medicine, University of Perugia, Perugia, Italy

    Matteo Pirro

  7. Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, 91779-48564, Iran

    Amirhossein Sahebkar

  8. Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia

    Amirhossein Sahebkar

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  1. Amir Abbas Momtazi
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  2. Fahimeh Shahabipour
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  3. Sepideh Khatibi
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  4. Thomas P. Johnston
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  6. Amirhossein Sahebkar
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Correspondence to Amirhossein Sahebkar .

Editor information

Editors and Affiliations

  1. KU Leuven, Leuven, Belgium

    Bernd Nilius

  2. Cardiovascular Research Center, Loyola University Chicago, Maywood, Illinois, USA

    Pieter de Tombe

  3. Walther-Straub-Institut für Pharmakologie und Toxikologie, München, Bayern, Germany

    Thomas Gudermann

  4. Department of Neurobiology, Max-Planck-Institute, Göttingen, Niedersachsen, Germany

    Reinhard Jahn

  5. Department of Cytobiology, University of Marburg, Marburg, Germany

    Roland Lill

  6. Cardiff School of Biosciences, Cardiff University, Cardiff, United Kingdom

    Ole H. Petersen

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Momtazi, A.A., Shahabipour, F., Khatibi, S., Johnston, T.P., Pirro, M., Sahebkar, A. (2016). Curcumin as a MicroRNA Regulator in Cancer: A Review. In: Nilius, B., de Tombe, P., Gudermann, T., Jahn, R., Lill, R., Petersen, O. (eds) Reviews of Physiology, Biochemistry and Pharmacology, Vol. 171. Reviews of Physiology, Biochemistry and Pharmacology, vol 171. Springer, Cham. https://doi.org/10.1007/112_2016_3

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