Abstract
Tagitinin C, a major sesquiterpenoid, was isolated from the leaves of Tithonia diversifolia. The high morbidity and mortality rate of hepatoma in Taiwan motivated our interest in the investigation of tagitinin C’s mechanism against the human hepatocellular carcinoma. The methanolic extract of leaves of T. diversifolia (TDM) and tagitinin C were found to have cytotoxic activities against human hepatoma Hep-G2 cells in the MTT assay with IC50 values of 40.0 ± 2.0 and 2.0 ± 0.1 μg/mL, respectively. This compound induced population increase in the sub-G1 phase and S phase arrest. Treatment with tagitinin C isolated from TDM resulted in activation of both caspase 3 and caspase 8 which suggested that the antiproliferative effect of this compound was caspase-dependent apoptosis. Magnetic resonance techniques indicated that the tumorigenisity of xenografts derived from Hep-G2 cells was retarded by the delivery of tagitinin C (15 μg/mouse/day) relative to the control counterparts.
Similar content being viewed by others
References
Lin CC, Lin ML, Lin JM (1993) The antiinflammatory and liver protective effect of Tithonia diversifolia (Hemsl.) Gray and Dicliptera chinensis Juss. Extracts in rats. Phytother Res 7:305–309
Rungeler P, Lyss G, Castro V, Mora G, Pahl HL, Merfort I (1998) Study of three sesquiterpene lactones from Tithonia diversifolia on their anti-inflammatory activity using the transcription factor NF-kappa B and enzymes of the arachidonic acid pathway as targets. Planta Med 64:588–593
Tona L, Kambu K, Mesia K, Cimanga K, Apers S, De Bruyne T, Pieters L, Totte J, Vlietinck AJ (1999) Biological screening of traditional preparations from some medicinal plants used as antidiarrheal in Kinshasa, Congo. Phytomedicine 6:59–66
Tona L, Kambu K, Ngimbi N, Mesia K, Penge O, Lusakibanza M, Cimanga K, De Bruyne T, Apers S, Totte J, Pieters L, Vlietinck AJ (2000) Antiamoebic and spasmolytic activities of extracts from some antidiarrheal traditional preparations used in Kinshasa, Congo. Phytomedicine 7:31–38
Kuo YH, Lin BY (1999) Five new taraxastane-type triterpenes from the aerial roots of Ficus microcarpa. Chem Pharm Bull 47:498–500
Kuo YH, Chen CH (1998) Sesquiterpenes from the leaves of Tithonia diversifolia. J Nat Prod 61:827–828
Kuo YH, Chen CH (1997) Diversifolia sesquiterpenes from the leaves of Tithonia diversifolia. Chem Pharm Bull 45:1223–1224
Bordoloi M, Barua NC, Ghosh AC (1996) An artemisinic acid analogue from Tithonia diversifolia. Phytochemistry 1:557–559
Baruah NC, Sarma JC, Barua NC, Sarma S, Sharma RP (1994) Germination and growth inhibitory sesquiterpene lactones and a flavone from Tithonia diversifolia. Phytochemistry 36:29–36
Schuster A, Stokes S, Papastergiou F, Castro V, Poveda L, Jakupovic J (1992) Sesquiterpene lactones from two Tithonia species. Phytochemistry 31:3139–3141
Chowdury PK, Barua NC, Sharma RP, Thyagarajan G, Herz W (1980) Structure of deacetylviguiestenin (tagitinin E). An addendum. J Org Chem 5:535–536
Baruah NC, Sharma RP, Madhusudanan KP, Thyagarajan G, Herz W, Murari R (1979) Sesquiterpene lactones of Tithonia diversifolia. Stereochemistry of the tagitinins and related compounds. J Organic Chem 44:1831–1835
Gu JQ, Gills JJ, Park EJ, Mata-Greenwood E, Hawthorne ME, Axelrod F, Chavez PI, Fong HH, Mehta RG, Pezzuto JM, Kinghorn AD (2002) Sesquiterpenoids from Tithonia diversifolia with potential cancer chemopreventive activity. J Nat Prod 65:532–536
Kuroda M, Yokosuka A, Kobayashi R, Jitsuno M, Kando H, Nosaka K, Ishii H, Yamori T, Mimaki Y (2007) Sesquiterpenoids and flavonoids from the aerial parts of Tithonia diversifolia and their cytotoxic activity. Chem Pharm Bull 55:1240–1244
Liao MH, Lin WC, Wen HC, Pu HF (2011) Tithonia diversifolia and its main active component tagitinin C induce survivin inhibition and G2/M arrest in human malignant glioblastoma cells. Fitoterapia 82:331–341
Lee MY, Liao MH, Tsai YN, Chiu KH, Wen HC (2011) Identification and anti-human glioblastoma activity of tagitinin C from Tithonia Diversifolia methanolic extract. J Agr Food Chem 59:2347–2355
Kaur P, Shukla S, Gupta S (2008) Plant flavonoid apigenin inactivates Akt to trigger apoptosis in human prostate cancer: an in vitro and in vivo study. Carcinogenesis 29:2210–2217
Kessel D, Luo Y (2000) Cells in cryptophycin-induced cell-cycle arrest are susceptible to apoptosis. Cancer Lett 151:25–29
Hu YW, Liu CY, Du CM, Zhang J, Wu WQ, Gu ZL (2009) Induction of apoptosis in human hepatocarcinoma SMMC-7721 cells in vitro by flavonoids from Astragalus complanatus. J Ethnopharmacol 123:293–301
Hengartner MO (2000) The biochemistry of apoptosis. Nature 407:770–776
Cai J, Zhao XL, Liu AW, Nian H, Zhang SH (2011) Apigenin inhibits hepatoma cell growth through alteration of gene expression patterns. Phytomedicine 18:366–373
Bizzi A, Movsas B, Tedeschi G, Phillips CL, Okunieff P, Alger JR, Di Chiro G (1995) Response of non-Hodgkin lymphoma to radiation therapy: early and long-term assessment with H-1 MR spectroscopic imaging. Radiology 194:271–276
Schwarz AJ, Maisey NR, Collins DJ, Cunningham D, Huddart R, Leach MO (2002) Early in vivo detection of metabolic response: a pilot study of 1H MR spectroscopy in extracranial lymphoma and germ cell tumours. Br J Radiol 75:959–966
Radermachera KA, Magata J, Bouzinc C, Laurentb S, Dresselaersd T, Himmelreichd U, Boutryb S, Mahieub I, Vander Elstb L, Feronc O, Mullerb RN, Jordana BF, Galleza B (2011) Multimodal assessment of early tumor response to chemotherapy: comparison between diffusion-weighted MRI, 1H-MR spectroscopy of choline and USPIO particles targeted at cell death. NMR Biomed. doi:10.1002/nbm.1765
Acknowledgments
We thank Professor Jiunn-Guang Lo for his technical assistance of semipreparative HPLC, Professor Kong-Hwa Chiu for his chemical identification support, Yang-Kao Wang, Research Assistant Investigator, Department of Medicine, Skeleton-Joint Research Center, National Cheng-Kung University Medical College, Tainan, Taiwan for his discussion and Mackay Memorial Hospital Hsin Chu Branch for the assistance with magnetic resonance imaging and magnetic resonance spectroscopy. This work was supported by grants from the National Science Council of the Republic of China (Grant NSC 97-2113-M-264-001 and Grant NSC 98-2622-M-264-002-CC3).
Author information
Authors and Affiliations
Corresponding author
Additional information
M.-H. Liao and Y.-N. Tsai contributed equally to this work.
Rights and permissions
About this article
Cite this article
Liao, MH., Tsai, YN., Yang, CY. et al. Anti-human hepatoma Hep-G2 proliferative, apoptotic, and antimutagenic activity of tagitinin C from Tithonia diversifolia leaves. J Nat Med 67, 98–106 (2013). https://doi.org/10.1007/s11418-012-0652-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11418-012-0652-0