title: Suppression of prostate cancer progression by cancer cell stemness inhibitor napabucasin.
abstract: A small population of cells with stem cell-like properties in prostate cancer (PCa), called prostate cancer stem cells (PrCSCs) or prostate stemness-high cancer cells, displays highly tumorigenic and metastatic features and may be responsible for the therapy resistance. A small molecule, napabucasin (BBI608), recently have been identified with suppression of stemness-high cancer cells in a variety of cancers. However, the effects of napabucasin on PCa cells as well as PrCSCs isolated from PCa cells have not yet been defined. The effect of napabucasin on PCa cells in cell proliferation, colony formation, and cell migration in vitro were measured by MTS, colony formation assay, and Transwell, respectively. Flow cytometry was employed to evaluate cell cycle and cell apoptosis, and the effect on tumorigenesis in vivo was examined by tumor growth assays. Furthermore, the role of napabucasin on self-renewal and survival of PrCSCs was evaluated by their ability to grow spheres and cell viability assay, respectively. Western Blot and qRT-PCR were used to determine the effect of napabucasin on the expressions of stemness markers. Decrease in cell viability, colony formation, migration, and survival with cell cycle arrest, higher sensitivity to docetaxel in vitro, and repressed tumorigenesis in vivo was observed upon napabucasin treatment. More importantly, napabucasin can obviously inhibit spherogenesis and even kill PrCSCs in vitro. Downregulation of stemness markers was observed after PrCSCs were treated with napabucasin. This study demonstrates that napabucasin may be a novel approach in the treatment of advanced PCa, specifically for castration-resistant prostate cancer (CRPC).
authors.affiliation: Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Clinical Medicine of Guangdong Pharmaceutical University, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Respiratory, The Third Affiliated Hospital of GuangZhou Medical University, GuangZhou Medical University, Guangzhou, China.
authors.forename: Xueting
authors.initials: X
authors.lastname: Ou
authors.affiliation: Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yawen
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Hulin
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Bingkun
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D051379:Mice; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors; D043823:Taxoids / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D050796:STAT3 Transcription Factor; D043823:Taxoids; D000077143:Docetaxel
keywords: Cancer cell stemness inhibitor; chemotherapy; napabucasin; prostate cancer; stemness-high cancer cells