A Novel Ginseng Saponin Metabolite-Induced Apoptosis in MHCC97-H Cells Involves Mitochondria-Mediated Pathway And Fas/Fasl Pathway Cross-Talking

摘要

Ginseng radix,the root of Panax ginseng C.A.Meyer,has been used as a crude drug taken orally for preventive and therapeutic purposes in Asian countries for thousands of years.In current,a novel intestinal bacterial metabolite of ginseng protopanaxadiol saponins,20-O-(β-D-glucopyranosyl )-20(S)-protopanaxadiol (IH-901),has been reported to induce apoptosis in a variety of cancer cells.Here,the in vitro antitumor activity of the compound was estimated by MTT assay in MHCC97-H cells.The results showed that IH-901 inhibits cell growth in a concentration-and time-dependent manner.In order to examine the mechanism of growth suppression by IH-901,MHCC97-H cell lines were selected to analyze for cell cycle progression by flow cytometry and for morphology change by Hoechst 33258 and AO/EB stain.We had observed that the increase in apoptotic sub-G1 fraction and apoptotic morphology change was evident in a concentration-dependent manner.We also observed the IH-901-induced cell cycle arrest at the G0-G1 phase and a progressive decline of S phase.cells occurred in cell.These results suggest that IH-901 induced apoptotic cell death concurrent with cell cycle arrest in MHCC97-H cells.In the molecular level,our study demonstrated that IH-901 up-regulates caspase-3 and caspase-9 protein expression in a dose-dependent manner,accompanied with the up-regulation of Fas and FasL protein expression.In conclusion,IH-901 could significantly inhibits cell proliferation and induce apoptosis in human MHCC97-H cells which involves mitochondrial-mediated pathway and Fas/FasL pathway cross-talking.