Saikosaponin-d inhibits proliferation of DU145 human prostate cancer cells by inducing apoptosis and arresting the cell cycle at G0/G1 phase

Abstract

Saikosaponin-d (SSd), a triterpene saponin compound derived from Bupleurum radix, has been shown to have a cytotoxic effect on various cancer cell lines. However, its effect on prostate cancer cells has remained unexplored. The present study reports the apoptosis-inducing effect of SSd on the DU145 human prostate carcinoma cell line. Treatment with SSd inhibited DU145 cell proliferation in a concentration-dependent manner. Flow cytometric analysis showed that SSd inhibited the proliferation of DU145 cells by induction of apoptosis and cell cycle arrest at G0/G1 phase. Further mechanistic experiments demonstrated that SSd arrested the cell cycle at G0/G1 phase via upregulation of p53 and p21 and induced apoptosis by modulating B-cell lymphoma 2 family proteins, dissipation of the mitochondrial membrane potential, release of cytochrome c into the cytosol and activation of caspase-3. In conclusion the present study indicated that SSd induced apoptosis in DU145 cells by the intrinsic apoptotic pathway. Therefore, SSd may become a leading candidate drug for the therapy of prostate carcinoma.