Saikosaponin-d: A potential chemotherapeutics in castration resistant prostate cancer by suppressing cancer metastases and cancer stem cell phenotypes.

Abstract

Androgen deprivation therapy is the gold standard regimen for advanced Prostate cancer (PCa) patients, nevertheless, patients eventually develop into castration-resistant prostate cancer (CRPC). Currently only a few chemotherapeutics are available for CRPC. Therefore, it is critical for identifying a new drug. In this study, we will explore a new agent, Saikosaponin-d (SSd), for CRPC therapy based on its mechanism of action. DU145 and CWR22Rv1 cells representing CRPC were employed in this study. A series of cell, biochemical, and molecular biologic assays such as Immunofluorescence, Zymography, Sphere formation, Colony formation, and MTT were used. Finally, we find SSd can significantly inhibit the growth of PCa cells in both dose- and time-dependent and suppress the colony formation during a long-term drug administration, it also can inhibit their migration and invasion abilities, which was accompanied by reverse the epithelial-mesenchymal transition (EMT) and suppress MMP2/9 expression as well as activities. Furthermore, SSd can suppress cancer stem cell (CSC) phenotypes such as self-renewal ability. Mechanistically, SSd blocks Wnt/β-catenin signaling pathway by decreasing GSK3β phosphorylation to affect EMT and CSC. These findings demonstrate the mechanism of anti-cancer activity of SSd in targeting EMT and CSC, suggesting SSd can be a potent agent for CRPC therapy.

• Authors: Di Zhong, Hui-Jian Zhang, Yao-Dong Jiang, Peng Wu, Huan Qi, Chao Cai, Shao-Bin Zheng, Qiang Dang
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 474 Issue 4 Pg. 722-729 (06 10 2016) ISSN: 1090-2104 [Electronic] United States
• PMID: 27155154 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Saponins
• Oleanolic Acid
• saikosaponin D

Topics

• Antineoplastic Agents, Phytogenic (administration & dosage)
• Apoptosis (drug effects)
• Carcinoma (pathology, prevention & control, secondary)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Feasibility Studies
• Humans
• Male
• Neoplasm Invasiveness
• Neoplastic Stem Cells (drug effects, pathology)
• Oleanolic Acid (administration & dosage, analogs & derivatives)
• Prostatic Neoplasms, Castration-Resistant (drug therapy, pathology)
• Saponins (administration & dosage)