Suppression of prostate cancer progression by cancer cell stemness inhibitor napabucasin

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...

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Main Authors:	Zhang, Yiming, Jin, Zhong, Zhou, Huimin, Ou, Xueting, Xu, Yawen, Li, Hulin, Liu, Chunxiao, Li, Bingkun
Format:	Online
Language:	English
Published:	John Wiley and Sons Inc. 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924383/

id	pubmed-4924383
recordtype	oai_dc
spelling	pubmed-49243832016-06-29 Suppression of prostate cancer progression by cancer cell stemness inhibitor napabucasin Zhang, Yiming Jin, Zhong Zhou, Huimin Ou, Xueting Xu, Yawen Li, Hulin Liu, Chunxiao Li, Bingkun Cancer Biology 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). John Wiley and Sons Inc. 2016-02-21 /pmc/articles/PMC4924383/ /pubmed/26899963 http://dx.doi.org/10.1002/cam4.675 Text en © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Zhang, Yiming Jin, Zhong Zhou, Huimin Ou, Xueting Xu, Yawen Li, Hulin Liu, Chunxiao Li, Bingkun
spellingShingle	Zhang, Yiming Jin, Zhong Zhou, Huimin Ou, Xueting Xu, Yawen Li, Hulin Liu, Chunxiao Li, Bingkun Suppression of prostate cancer progression by cancer cell stemness inhibitor napabucasin
author_facet	Zhang, Yiming Jin, Zhong Zhou, Huimin Ou, Xueting Xu, Yawen Li, Hulin Liu, Chunxiao Li, Bingkun
author_sort	Zhang, Yiming
title	Suppression of prostate cancer progression by cancer cell stemness inhibitor napabucasin
title_short	Suppression of prostate cancer progression by cancer cell stemness inhibitor napabucasin
title_full	Suppression of prostate cancer progression by cancer cell stemness inhibitor napabucasin
title_fullStr	Suppression of prostate cancer progression by cancer cell stemness inhibitor napabucasin
title_full_unstemmed	Suppression of prostate cancer progression by cancer cell stemness inhibitor napabucasin
title_sort	suppression of prostate cancer progression by cancer cell stemness inhibitor napabucasin
description	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).
publisher	John Wiley and Sons Inc.
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924383/
_version_	1613600774085935104

Suppression of prostate cancer progression by cancer cell stemness inhibitor napabucasin

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