Anti-proliferation of MDA-MB-231 cells by Averrhoa bilimbi extract is associated with G0/G1 perturbation and mitochondria-mediated apoptosis independent of p53

Practiced as folk medicine since ancient times, bilimbi (Averrhoa bilimbi) is commonly consumed and widely cultivated in Malaysia. In search for naturally occurring anticancer agents, a potential fruit extract was found to exert anticancer properties in vitro without any cytotoxic effect on normal cells. This study investigated the anti-proliferative effect and underlying cell death pathway induced by bilimbi ethanolic extract on human non-hormone-dependent breast cancer cell line, MDA-MB-231. Anticancer potential of bilimbi extract was conducted by investigating the in vitro growth inhibitory effect, DNA fragmentation, cell cycle progression and anti-proliferation assay. Release of caspases, cytochrome c and apoptotic proteins were demonstrated to determine the mechanism of cell death pathway. Findings revealed that bilimbi inhibited growth of MDA-MB-231 cells through the induction of apoptosis mediated by cell cycle arrest at G0/G1 checkpoint. Released of cytochrome c coupled with up-regulation of caspase-3/7, caspase-9 and Bax pro-apoptotic proteins in addition to down-regulation of dysfunctional p53 and Bcl-2 anti-apoptotic proteins implied that bilimbi induced a p53-independent mitochondrial apoptosis pathway in MDA-MB-231. These results suggest that bilimbi could induce tumor cell anti-proliferation through apoptosis. As a natural product, bilimbi could be a promising anticancer agent and an inexpensive approach to cancer chemoprevention strategy