Antiproliferation effect and apoptosis mechanism of prostate cancer cell PC-3 by flavonoids and saponins prepared from Gynostemma pentaphyllum.

The objectives of this study were to investigate the antiproliferation and apoptosis mechanism of saponin and flavonoid fractions from Gynostemma pentaphyllum (Thunb.) Makino on prostate cancer cell PC-3. Both flavonoid and saponin fractions were isolated by a column chromatographic method with Cosmosil 75C(18)-OPN as adsorbent and elution solvents of ethanol-water (30:70, v/v) for the former and 100% ethanol for the latter, followed by high-performance liquid chromatography-tandem mass spectrometry analysis. On the basis of the MTT assay, the saponin and flavonoid fraction were comparably effective in inhibiting the growth of PC-3 cells, with the IC(50) being 39.3 and 33.3 μg/mL, respectively. Additionally, both fractions induced an arrest of PC-3 cell cycle at both S and G2/M phases, with both early and late apoptotic cell populations showing a dose-dependent rise. The Western blot assay indicated that the incorporation of flavonoid or saponin fraction could modulate the expression of G2 and M checkpoint regulators, cyclins A and B, and the antiapoptotic proteins Bcl-2 and Bcl-xl and pro-apoptotic proteins Bad and Bax. The expression of the caspase-3 and its activated downstream substrate effectors, DFF45 and poly (ADP-ribose) polymerase-1 (PARP-1), was also increased and followed a dose-dependent manner. All of these findings suggest that the apoptosis of PC-3 cells may proceed through the intrinsic mitochondria pathway.