1. Academic Validation
  2. Suppression of prostate cancer progression by cancer cell stemness inhibitor napabucasin

Suppression of prostate cancer progression by cancer cell stemness inhibitor napabucasin

  • Cancer Med. 2016 Jun;5(6):1251-8. doi: 10.1002/cam4.675.
Yiming Zhang 1 Zhong Jin 1 Huimin Zhou 2 Xueting Ou 3 Yawen Xu 1 Hulin Li 1 Chunxiao Liu 1 Bingkun Li 1
Affiliations

Affiliations

  • 1 Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
  • 2 Department of Gastroenterology, The First Affiliated Hospital of Clinical Medicine of Guangdong Pharmaceutical University, Guangdong Pharmaceutical University, Guangzhou, China.
  • 3 Department of Respiratory, The Third Affiliated Hospital of GuangZhou Medical University, GuangZhou Medical University, Guangzhou, China.
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).

Keywords

Cancer cell stemness inhibitor; chemotherapy; napabucasin; prostate cancer; stemness-high cancer cells.

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  • HY-13919
    98.85%, STAT3 Inhibitor