Ginsenoside Rg3 induces Apoptosis of human breast cancer (MDA-MB-231) cells

Abstract

Background: Rg3, a major ginsenoside derived from heat-processed ginseng, has been reported to have anti-inflammatory andanti-proliferative activities. In our previous studies, Rg3 inhibited phorbol ester-induced cyclooxygenase-2 expression and NF-κBactivation in cultured human mammary epithelial (MCF-10A) cells and in mouse skin in vivo. In this study, we investigatedRg3-induced apoptosis in human breast cancer (MDA-MB-231) cells and underlying molecular mechanisms. Methods: After Rg3 treatment, apoptotic cell death of MDA-MB-231 cell was investigated by the MTT reduction assay andmeasurement of the mitochondrial membrane depolarization. Flow cytometry was used for cell cycle analysis and detection ofapoptotic cells as well as measurement of reactive oxygen species. Expression of apoptotic-related proteins was determined byimmunoblot analysis. Results: MDA-MB-231 cells treated with Rg3 (30μM) exhibited the increased proportion of hypodiploid or apoptotic cells. Rg3treatment resulted in an increase in the ratio of proapoptotic Bax to antiapoptotic Bcl-2, depolarization of the mitochondriamembrane potential and the release of cytochrome c from mitochondria. Rg3 also induced the proteolytic cleavage of caspase-3and poly (ADP-ribose) polymerase, which was attenuated by a caspase-3 inhibitor, z-VAD-fmk. Conclusions: Based on these findings, it is likely that Rg3 induces apoptosis in MDA-MB-231 cells via classicalmitochondria-dependent caspase activation. These data suggest that Rg3 might be a potential candidate as a breast cancerchemopreventive agent.