Anti-proliferating effects of ginsenoside Rh2 on MCF-7 human breast cancercells

Ginsenoside Rh2 (G-Rh2) isolated from the root of Panax ginseng has been sh own to have anti-cancer proliferation, differentiation and chemopreventive effects in certain cancer cell types. We investigated the mechanism of G-Rh 2-induced growth inhibition in MCF-7 human breast carcinoma cells. G-Rh2 si gnificantly inhibited the cell growth in a concentration-dependent manner, which effect was reversible, and induced a G1 arrest in cell cycle progress ion. G-Rh2 treatment down-regulated the protein level of cyclin D3 but upre gulated the expression of cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/ CIP1). The increased levels of p21 were associated with increased binding o f p21 and Cdk2 concomitant with marked decrease in Cdk2 and cyclin E-depend ent kinase activities with no changes in Cdk2 and cyclin E expression. G-Rh 2 markedly reduced the phosphorylated retinoblastoma protein (pRb) and ench anced association of unphosphorylated pRb and the transcription factor E2F- 1. These data suggest that G-Rh2 inhibited the growth of MCF-7 cells, by in ducing protein expression of p21 and reducing the protein levels of cyclin D which resulted in the down-regulation of cyclin/Cdk complex kinase activi ty, decreasing phosphorylation of pRb, and inhibiting E2F release.