Ginsenoside-Rh2 blocks the cell cycle of SK-HEP-1 cells at the G1/S boundary by selectively inducing the protein expression of p27kip1

The mechanism of action by which ginsenoside-Rh2 (G-Rh2) suppresses the proliferation of SK-HEP-1 cells is reported. The results from flow cytometric analyses show that G-Rh2 arrested the cell cycle at the G1/S transition phase. The cyclin E-dependent kinase activity which had been immunoprecipitated with cyclin E-specific antibody was down-regulated in the cells in response to G-Rh2. The IC50 value required to down-regulate the kinase activity by 50% was approximately 0.75 microM. Immunoblotting analyses show that G-Rh2 selectively induced the expression of p27kip1 in a dose-dependent manner whereas it had no effect on the levels of cyclin E, cdk2, and p21WAF1. In addition, our data show that G-Rh2 reduced the protein levels of cdc25A at doses higher than 10 microM. Collectively, these data suggest that ginsenoside-Rh2 arrests the cell cycle at the G1/S transition phase by selectively inducing protein expression of p27Kip1 and, as a consequence, down-regulating cyclin E-dependent kinase activity.