Journal
JOURNAL OF ETHNOPHARMACOLOGY
Volume 142, Issue 1, Pages 72-79Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jep.2012.04.015
Keywords
Wrightia tomentosa; Breast cancer; Apoptosis; Oleanolic acid; Ursolic acid
Categories
Funding
- CSIR, New Delhi
- Ministry of Health and Family Welfare, Government of India
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Ethnopharmacological relevance: Wrightia tomentosa Roem. & Schult. (Apocynaceae) is known in the traditional medicine for anti-cancer activity along with other broad indications like snake and scorpion bites, renal complications, menstrual disorders etc. However, the anti-cancer activity of this plant or its constituents has never been studied systematically in any cancer types so far. Aim of the study: To evaluate the anti-cancer activities of the ethanolic extract of W. tomentosa and identified constituent active molecule(s) against breast cancer. Material and methods: Powdered leaves of W. tomentosa were extracted with ethanol. The ethanolic extract, subsequent hexane fractions and fraction F-4 of W. tomentosa were tested for its anti-proliferative and pro-apoptotic effects in breast cancer cells MCF-7 and MDA-MB-231. Results: The ethanolic extract, subsequent hexane fractions and fraction F-4 of W. tomentosa inhibited the proliferation of human breast cancer cell lines, MCF-7 and MDA-MB-231. The fraction F-4 obtained from hexane fraction inhibited proliferation of MCF-7 and MDA-MB-231 cells in concentration and time dependent manner with IC50 of 50 mu g/ml and 30 mu g/ml for 24 h, 28 mu g/ml and 22 mg/ml for 48 h and 25 mu g/ml and 20 mu g/ml for 72 h respectively. The fraction F-4 induced Cl cell cycle arrest, reactive oxygen species (ROS) generation, loss of mitochondrial membrane potential and subsequent apoptosis. Apoptosis is indicated in terms of increased Bax/Bcl-2 ratio, enhanced Annexin-V positivity, caspase 8 activation and DNA fragmentation. The active molecule isolated from fraction F-4, oleanolic acid and urosolic acid inhibited cell proliferation of MCF-7 and MDA-MB-231 cells at IC50 value of 7.5 mu M and 7.0 mu M respectively, whereas there is devoid of significant cell inhibiting activity in non-cancer originated cells, HEK-293. In both MCF-7 and MDA-MB-231, oleanolic acid and urosolic acid induced cell cycle arrest and apoptosis as indicated by significant increase in Annexin-V positive apoptotic cell counts. Conclusion: Our results suggest that W. tomentosa extracts has significant anti-cancer activity against breast cancer cells due to induction of apoptosis pathway. Olenolic and urosolic acid are important constituent molecules in the extract responsible for anti-cancer activity of W. tomentosa. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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