title: 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.affiliation: Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhong
authors.affiliation: Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Hui-Jian
authors.initials: HJ
authors.lastname: Zhang
authors.affiliation: Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Yao-Dong
authors.initials: YD
authors.lastname: Jiang
authors.affiliation: Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Qi
authors.affiliation: Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Cai
authors.affiliation: Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China. Electronic address: 270649181@qq.com.
authors.forename: Shao-Bin
authors.initials: SB
authors.lastname: Zheng
authors.affiliation: Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China. Electronic address: jasondang@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Dang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology*; D012503:Saponins / Q000008:administration & dosage*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012503:Saponins; D009828:Oleanolic Acid; C025759:saikosaponin D
keywords: Cancer stem cell; EMT; Prostate cancer; Saikosaponin-d; Wnt