9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer

Abstract Glycogen synthase kinase-3 beta (GSK-3β), a serine/threonine kinase, has been identified as a potential therapeutic target in human bladder cancer. In the present study, we investigated the antitumor effect of a small molecule GSK-3β inhibitor, 9-ING-41, currently in clinical studies in pat...

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Autores principales:	Hiroo Kuroki, Tsutomu Anraku, Akira Kazama, Vladimir Bilim, Masayuki Tasaki, Daniel Schmitt, Andrew P. Mazar, Francis J Giles, Andrey Ugolkov, Yoshihiko Tomita
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1423d830529042219401ce10296db960
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spelling	oai:doaj.org-article:1423d830529042219401ce10296db9602021-12-02T13:35:03Z9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer10.1038/s41598-019-56461-42045-2322https://doaj.org/article/1423d830529042219401ce10296db9602019-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-56461-4https://doaj.org/toc/2045-2322Abstract Glycogen synthase kinase-3 beta (GSK-3β), a serine/threonine kinase, has been identified as a potential therapeutic target in human bladder cancer. In the present study, we investigated the antitumor effect of a small molecule GSK-3β inhibitor, 9-ING-41, currently in clinical studies in patients with advanced cancer, in bladder cancer cell lines. We found that treatment with 9-ING-41 leads to cell cycle arrest, autophagy and apoptosis in bladder cancer cells. The autophagy inhibitor chloroquine potentiated the antitumor effects of 9-ING-41 when tested in combination studies. Our findings also demonstrate that 9-ING-41 enhanced the growth inhibitory effects of gemcitabine or cisplatin when used in combination in bladder cancer cells. Finally, we found that 9-ING-41 sensitized bladder cancer cells to the cytotoxic effects of human immune effector cells. Our results provide a rationale for the inclusion of patients with advanced bladder cancer in clinical studies of 9-ING-41.Hiroo KurokiTsutomu AnrakuAkira KazamaVladimir BilimMasayuki TasakiDaniel SchmittAndrew P. MazarFrancis J GilesAndrey UgolkovYoshihiko TomitaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-9 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hiroo Kuroki Tsutomu Anraku Akira Kazama Vladimir Bilim Masayuki Tasaki Daniel Schmitt Andrew P. Mazar Francis J Giles Andrey Ugolkov Yoshihiko Tomita 9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer
description	Abstract Glycogen synthase kinase-3 beta (GSK-3β), a serine/threonine kinase, has been identified as a potential therapeutic target in human bladder cancer. In the present study, we investigated the antitumor effect of a small molecule GSK-3β inhibitor, 9-ING-41, currently in clinical studies in patients with advanced cancer, in bladder cancer cell lines. We found that treatment with 9-ING-41 leads to cell cycle arrest, autophagy and apoptosis in bladder cancer cells. The autophagy inhibitor chloroquine potentiated the antitumor effects of 9-ING-41 when tested in combination studies. Our findings also demonstrate that 9-ING-41 enhanced the growth inhibitory effects of gemcitabine or cisplatin when used in combination in bladder cancer cells. Finally, we found that 9-ING-41 sensitized bladder cancer cells to the cytotoxic effects of human immune effector cells. Our results provide a rationale for the inclusion of patients with advanced bladder cancer in clinical studies of 9-ING-41.
format	article
author	Hiroo Kuroki Tsutomu Anraku Akira Kazama Vladimir Bilim Masayuki Tasaki Daniel Schmitt Andrew P. Mazar Francis J Giles Andrey Ugolkov Yoshihiko Tomita
author_facet	Hiroo Kuroki Tsutomu Anraku Akira Kazama Vladimir Bilim Masayuki Tasaki Daniel Schmitt Andrew P. Mazar Francis J Giles Andrey Ugolkov Yoshihiko Tomita
author_sort	Hiroo Kuroki
title	9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer
title_short	9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer
title_full	9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer
title_fullStr	9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer
title_full_unstemmed	9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer
title_sort	9-ing-41, a small molecule inhibitor of gsk-3beta, potentiates the effects of anticancer therapeutics in bladder cancer
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/1423d830529042219401ce10296db960
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9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer

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