Paris saponin II of Rhizoma Paridis--a novel inducer of apoptosis in human ovarian cancer cells.

Rhizoma Paridis (dried root and rhizome) has been an essential ingredient in traditional Chinese herbal medicine. In the past decade, active components of Rhizoma Paridis - the Paris saponins have emerged as promising anti-cancer agents. Among these saponins, polyphyllin D (Paris saponin (PS) I), has been extensively studied and proposed to be a potent antitumor agent. In this study, we continue to establish the efficacy and mechanisms underlying the cytotoxic effects of the steroidal PS members, namely formosanin C (PSII) in ovarian cancer treatment. We isolated PSII and evaluated its effects on a panel of ten human cell lines. Isolated PSII has potent inhibitory effects on the growth of tumor cells without deleterious effects to different normal cell types or benign neoplastic derived cells. While PSII, PSI, and etoposide are effective promoting agents for cell cycle arrest and apoptosis, PSII appeared to be marginally more potent than the later two in inhibiting SKOV3 cell growth. In PSII-treated SKOV3 cells, there was an elevation in proapoptotic elements including Bax, cytosolic cytochrome c, activated-caspase-3, and activated-caspase-9. The treatment also reduced extracellular signal-regulated kinase (ERK1/2) phosphorylation and anti-apoptotic Bcl-2 expression. We also assessed the antitumor efficacy of intraperitoneal administration of PSII in human SKOV3 ovarian cancer xenografts in athymic mice. PSII treatment significantly inhibited the growth of xenograft tumors relative to controls by 70% (p < 0.05). These findings demonstrated that, in addition to the unique selectivity against cancer cells, PSII is a potent antitumor molecule that may be developed as a cancer therapeutic agent.