Molecular mechanisms of ginsenoside Rp1-mediated growth arrest and apoptosis.

Ginsenoside Rpl, a semi-synthesized ginseng saponin, was shown to have chemopreventive action and anti-metastatic potential. However, the molecular mechanisms of Rpl on cell growth and death are not fully understood. In this study, the antiproliferative effect of Rp1 on HeLa cells in vitro was investigated. Treatment with Rp1 at 40 μM inhibited the proliferation and partial accumulation of cells at the G1 phase. Rp1-mediated G arrest was accompanied by decreased expression of cyclin D1, E, and A and increased expression of p21 without any significant change in p53 or phospho-p53 (Ser15). On the other hand, prolonged incubation with Rp1 at 40 μM caused apoptosis and activation of caspase-3, -8, and -9. The participation of these three caspases in apoptosis was more clearly shown in experiments using inhibitors, which markedly prevented Rpl-induced apoptosis in the case of each caspase. Cleavage of the polyADP-ribose polymerase, often used as an apoptotic marker, was also found in Rpl-induced apoptosis. Among Bcl-2 family proteins (Bad, Bax, Bid, Bcl-2), Bax and Bid were activated by Rpl treatment, which resulted in the release of cytochrome c from mitochondria, following activation of caspase-9. These observations indicate that multiple cell cycle regulatory proteins and apoptosis-inducing proteins are regulated by Rp1 and contribute to Rp1-induced growth arrest and apoptosis.