Casuarinin from the Bark of Terminalia arjuna Induces Apoptosis and Cell Cycle Arrest in Human Breast Adenocarcinoma MCF-7 Cells

Abstract

Casuarinin, a hydrolyzable tannin isolated from the bark of Terminalia arjuna L. (Combretaceae), was investigated for its antiproliferative activity in human breast adenocarcinoma MCF-7 cells. The results showed that casuarinin inhibited the proliferation of MCF-7 by blocking cell cycle progression in the G0/G1 phase and inducing apoptosis. An enzyme-linked immunosorbent assay showed that casuarinin increased the expression of p21/WAF1 concomitantly as the MCF-7 cells underwent G0/G1 arrest. An enhancement in Fas/APO-1 and its two forms of ligands, membrane-bound Fas ligand (mFasL) and soluble Fas ligand (sFasL), might be responsible for the apoptotic effect induced by casuarinin. Our study reports here for the first time that the induction of p21/WAF1 and the activity of Fas/Fas ligand apoptotic system may participate in the antiproliferative activity of casuarinin in MCF-7 cells.

Key words

Terminalia arjuna - Combretaceae - casuarinin - p53 - p21/WAF1 - Fas/APO-1 - Fas ligand - apoptosis

References

• 1 Brinton L, Lacey J, Devesa S S. Epidemiology of Breast Cancer. In: Donegan WL, Spratt JS (editors) Cancer of the Breast, 5th edition. Philadelphia; WB Saunders 2002: pp 111-32
• 2 Chie W C, Chang S H, Huang C S, Tzeng S J, Chen J H, Fan B Y, Chang K J. Prognostic factors for the survival of Taiwanese breast cancer patients.  J Formos Med Assoc. 2002;  101 98-103
• 3 Chopin V, Toillon R A, Jouy N, Le Bourhis X. p21(WAF1/CIP1) is dispensable for G1 arrest, but indispensable for apoptosis induced by sodium butyrate in MCF-7 breast cancer cells.  Oncogene. 2004;  23 21-9
• 4 Shaila H P, Udupa S L, Udupa A L. Hypolipidemic activity of three indigenous drugs in experimentally induced atherosclerosis.  Int J Cardiol. 1998;  67 119-24
• 5 Perumal Samy R, Ignacimuthu S, Sen A. Screening of 34 Indian medicinal plants for antibacterial properties.  J Ethnopharmacol. 1998;  62 173-82
• 6 Cheng H Y, Lin C C, Lin T C. Antiherpes simplex virus type 2 activity of casuarinin from the bark of Terminalia arjuna Linn.  Antiviral Res. 2002;  55 447-55
• 7 Yang L L, Lee C Y, Yen K Y. Induction of apoptosis by hydrolyzable tannins from Eugenia jambos L. on human leukemia cells.  Cancer Lett. 2000;  157 65-75
• 8 Ishii R, Saito K, Horie M, Shibano T, Kitanaka S, Amano F. Inhibitory effects of hydrolyzable tannins from Melastoma dodecandrum Lour. on nitric oxide production by a murine macrophage-like cell line, RAW264.7, activated with lipopolysaccharide and interferon-gamma.  Biol Pharm Bull. 1999;  22 647-53
• 9 Kashiwada Y, Nonaka G, Nishioka I, Chang J J, Lee K H. Antitumor agents, 129. Tannins and related compounds as selective cytotoxic agents.  J Nat Prod. 1992;  55 1033-43
• 10 Satomi H, Umemura K, Ueno A, Hatano T, Okuda T, Noro T. Carbonic anhydrase inhibitors from the pericarps of Punica granatum L.  Biol Pharm Bull. 1993;  16 787-90
• 11 Lin T C, Ma Y T, Hsu F L. Tannins from the bark of Terminalia arjuna .  Chin Pharm J. 1996;  48 25-35
• 12 Takahashi N, Li W, Banerjee D, Guan Y, Wada-Takahashi Y, Brennan M F, Chou T C, Scotto K W, Bertino J R. Sequence-dependent synergistic cytotoxicity of ecteinascidin-743 and paclitaxel in human breast cancer cell lines in vitro and in vivo .  Cancer Res. 2002;  62 6909-15
• 13 May P, May E. Twenty years of p53 research: structural and functional aspects of the p53 protein.  Oncogene. 1999;  18 7621-36
• 14 Harper J W, Adami G R, Wei N, Keyomarsi K, Elledge S J. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.  Cell. 1993;  75 805-16
• 15 Macleod K F, Sherry N, Hannon G, Beach D, Tokino T, Kinzler K, Vogelstein B, Jacks T. (1995). p53-dependent and independent expression of p21 during cell growth, differentiation, and DNA damage.  Genes Dev. 1995;  9 935-44
• 16 Brooks C L, Gu W. Ubiquitination, phosphorylation and acetylation: the molecular basis for p53 regulation.  Curr Opin Cell Biol. 2003;  15 164-71
• 17 Nagata S, Golstein P. The Fas death factor.  Science. 1995;  267 1449-56
• 18 Landowski T H, Gleason-Guzman M C, Dalton W S. Selection for drug resistance results in resistance to Fas-mediated apoptosis.  Blood. 1997;  89 1854-61
• 19 Gibson S, Tu S, Oyer R, Anderson S M, Johnson G L. Epidermal growth factor protects epithelial cells against Fas-induced apoptosis. Requirement for Akt activation.  J Biol Chem. 1999;  274 17 612-8
• 20 Reimer T, Herrnring C, Koczan D, Richter D, Gerber B, Kabelitz D, Friese K, Thiesen H J. FasL: Fas ratio - a prognostic factor in breast carcinomas.  Cancer Res. 2000;  15 822-8