Terrestrosin D, a steroidal saponin from Tribulus terrestris L., inhibits growth and angiogenesis of human prostate cancer in vitro and in vivo

Objective: The aim of this study was to investigate whether terrestrosin D (TED) inhibits the progression of castration-resistant prostate Cancer and consider its mechanism.

Methods: Cell cycle, mitochondrial membrane potential (ΔΨm) and Apoptosis were determined by flow cytometry. Caspase-3 activity and vascular endothelial growth factor secretion were detected by a Caspase-3 assay and human vascular endothelial growth factor kit, respectively. A PC-3 xenograft mouse model was used to evaluate the Anticancer effect of TED in vivo.

Results: In vitro, TED strongly suppressed the growth of prostate Cancer cells and endothelial cells in a dose-dependent manner. TED induced cell cycle arrest and Apoptosis in PC-3 cells and human umbilical vascular endothelial cells (HUVECs). TED-induced Apoptosis did not involve the Caspase pathway. TED also decreased ΔΨm in PC-3 cells and HUVECs. In vivo, TED significantly suppressed tumor growth in nude mice bearing PC-3 cells, without any overt toxicity. Immunohistochemical analysis showed TED induced apoptotic cell death and inhibited angiogenesis in xenograft tumor cells.

Conclusion: Cell cycle arrest and induction of Apoptosis in Cancer cells and endothelial cells might be plausible mechanisms of actions for the observed antitumor and antiangiogenic activities of TED.