GINSENOSIDE Rk1 INDUCES G2/M PHASE ARREST THROUGH SLOW ACTIVATION OF ERK IN HUMAN HEPATOCELLULAR CARCINOMA CELLS

Abstract

Ginsenoside Rk1 is one of the major components of heat-processed Panax ginseng. In a previous study, Rk1 showed anti-tumor activity via inhibition of telomerase activity and induction of apoptosis in human hepatocellular carcinoma cells. Hence, we investigated Rk1-mediated cell cycle regulation in HepG2 cell lines. The cells were treated with varying concentrations of Rk1 for different time periods. Rk1 treatment for 24 h led to a dose-dependent accumulation of cells at G1 phase. However, G2/M phase arrest was induced at a 100 μM concentration of Rk1 after 48 hrs. We focused on the time period (48 h) when G2/M phase arrest was triggered, because significant induction of apoptosis was detected for the same period in a previous study. Immunoblot analysis revealed a dose-dependent decrease in p53 and cyclin D1 protein levels by Rk1. Also, p21 was moderately decreased by Rk1 at concentrations of 50 to 75 μM. However, this trend was reversed at 100 μM Rk1. Especially, phosphorylation of extracellular-regulated kinase (ERK) was clearly induced at the same dose. These results suggest that the slow activation of ERK is related to Rk1 -mediated G2/M phase arrest and that the effect of Rk1 on cell cycle progression is also associated with induction of apoptosis in HepG2 cells and therefore can be used to develop new anti-hepatoma agents.