title: 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 and anti-proliferative activities. In our previous studies, Rg3 inhibited phorbol ester-induced cyclooxygenase-2 expression and NF-κB activation in cultured human mammary epithelial (MCF-10A) cells and in mouse skin in vivo. In this study, we investigated Rg3-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 and measurement of the mitochondrial membrane depolarization. Flow cytometry was used for cell cycle analysis and detection of apoptotic cells as well as measurement of reactive oxygen species. Expression of apoptotic-related proteins was determined by immunoblot analysis.
  
  
  RESULTS
  MDA-MB-231 cells treated with Rg3 (30μM) exhibited the increased proportion of hypodiploid or apoptotic cells. Rg3 treatment resulted in an increase in the ratio of proapoptotic Bax to antiapoptotic Bcl-2, depolarization of the mitochondria membrane potential and the release of cytochrome c from mitochondria. Rg3 also induced the proteolytic cleavage of caspase-3 and 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 classical mitochondria-dependent caspase activation. These data suggest that Rg3 might be a potential candidate as a breast cancer chemopreventive agent.
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University.
authors.forename: Bo-Min
authors.initials: BM
authors.lastname: Kim
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University.
authors.forename: Do-Hee
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University.
authors.forename: Jeong-Hill
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Food and Nutrition, Sungshin Women's University, Seoul, Korea.
authors.forename: Hye-Kyung
authors.initials: HK
authors.lastname: Na
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University.
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Surh
keywords: Apoptosis; Breast cancer; Ginsenoside; MDA-MB-231 cells; Rg3