Terrestrosin D, a Steroidal Saponin from Tribulus terrestris L., Inhibits Growth and Angiogenesis of Human Prostate Cancer in vitro and in vivo

• Published in: Pathobiology (Basel) Vol. 81; no. 3; pp. 123 - 132
• Main Authors: Wei, Shihu, Fukuhara, Hideo, Chen, Guang, Kawada, Chiaki, Kurabayashi, Atsushi, Furihata, Mutsuo, Inoue, Keiji, Shuin, Taro
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2014
• Subjects: Adenocarcinoma - blood supply; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Angiogenesis; Animals; Apoptosis; Apoptosis - drug effects; Caspase 3 - metabolism; Cell cycle; Cell Cycle - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Disease Models, Animal; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Heterografts; Humans; In Vitro Techniques; Male; Mice; Mice, Nude; Neovascularization, Pathologic - drug therapy; Original Paper; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Prostate cancer; Prostatic Neoplasms - blood supply; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Saponins - pharmacology; Saponins - therapeutic use; Tribulus; Vascular Endothelial Growth Factor A - metabolism; Xenograft Model Antitumor Assays; Steroidal saponin; Angiogenesis; Terrestrosin D; Apoptosis
• ISSN: 1015-2008; 1423-0291
• DOI: 10.1159/000357622

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.