Caspases are key mediators of apoptosis. Caspase-8 mediates extrinsic, and caspase-9 initiates the intrinsic pathway of apoptosis[3]. Ginsenoside Rh2 (G-Rh2), isolated from the root of Ginseng, is an activator of caspase-8 and caspase-9 and induces cancer cell apoptosis in a multi-path manner. The cell viability of the human tumor cell lines HeLa, SK-HEP-1, SW480, and PC-3 was remarkably inhibited by G-Rh2, with IC50s of 2.52, 3.15, 4.06 and 7.85 μg/mL, respectively. G-Rh2 might have the unique ability to simultaneously and independently activate both caspase-8 and caspase-9 in HeLa cells. In HeLa cells treated with 7.5 μg/mL G-Rh2 for 4 h, Fas (key factor for caspase-8 activation) and TNF-R1 were remarkably up-regulated by G-Rh2 in a time-dependent manner. Furthermore, significant increases in Fas expression and caspase-8 activity following G-Rh2 treatment coincided with an increase in p53 expression in p53-non-mutated HeLa and SK-HEP-1 cells indicating that G-Rh2 may act as a stabilizer for p53[4]. In male C57BL6 mice, the tumor sizes in the G-L group and G-H group (G-L and G-H refer to a low or high dose of G-Rh2 injection) were reduced compared with the tumor group. Moreover, the G-Rh2 treated mice survived longer than the untreated ones in a dose-dependent manner[5].
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