Modulating the unfolded protein response with ONC201 to impact on radiation response in prostate cancer cells

Abstract Prostate cancer (PCa) is the most common non-cutaneous cancer in men and a notable cause of cancer mortality when it metastasises. The unfolded protein response (UPR) can be cytoprotective but when acutely activated can lead to cell death. In this study, we sought to enhance the acute activ...

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Autores principales:	Francesca Amoroso, Kimberley Glass, Reema Singh, Francisco Liberal, Rebecca E. Steele, Sarah Maguire, Rohinton Tarapore, Joshua E. Allen, Sandra Van Schaeybroeck, Karl T. Butterworth, Kevin Prise, Joe M. O’Sullivan, Suneil Jain, David J. Waugh, Ian G. Mills
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e08cdcf6c9974257a805988e30144259
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spelling	oai:doaj.org-article:e08cdcf6c9974257a805988e301442592021-12-02T10:54:15ZModulating the unfolded protein response with ONC201 to impact on radiation response in prostate cancer cells10.1038/s41598-021-83215-y2045-2322https://doaj.org/article/e08cdcf6c9974257a805988e301442592021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83215-yhttps://doaj.org/toc/2045-2322Abstract Prostate cancer (PCa) is the most common non-cutaneous cancer in men and a notable cause of cancer mortality when it metastasises. The unfolded protein response (UPR) can be cytoprotective but when acutely activated can lead to cell death. In this study, we sought to enhance the acute activation of the UPR using radiation and ONC201, an UPR activator. Treating PCa cells with ONC201 quickly increased the expression of all the key regulators of the UPR and reduced the oxidative phosphorylation, with cell death occurring 72 h later. We exploited this time lag to sensitize prostate cancer cells to radiation through short-term treatment with ONC201. To understand how priming occurred, we performed RNA-Seq analysis and found that ONC201 suppressed the expression of cell cycle and DNA repair factors. In conclusion, we have shown that ONC201 can prime enhanced radiation response.Francesca AmorosoKimberley GlassReema SinghFrancisco LiberalRebecca E. SteeleSarah MaguireRohinton TaraporeJoshua E. AllenSandra Van SchaeybroeckKarl T. ButterworthKevin PriseJoe M. O’SullivanSuneil JainDavid J. WaughIan G. MillsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Francesca Amoroso Kimberley Glass Reema Singh Francisco Liberal Rebecca E. Steele Sarah Maguire Rohinton Tarapore Joshua E. Allen Sandra Van Schaeybroeck Karl T. Butterworth Kevin Prise Joe M. O’Sullivan Suneil Jain David J. Waugh Ian G. Mills Modulating the unfolded protein response with ONC201 to impact on radiation response in prostate cancer cells
description	Abstract Prostate cancer (PCa) is the most common non-cutaneous cancer in men and a notable cause of cancer mortality when it metastasises. The unfolded protein response (UPR) can be cytoprotective but when acutely activated can lead to cell death. In this study, we sought to enhance the acute activation of the UPR using radiation and ONC201, an UPR activator. Treating PCa cells with ONC201 quickly increased the expression of all the key regulators of the UPR and reduced the oxidative phosphorylation, with cell death occurring 72 h later. We exploited this time lag to sensitize prostate cancer cells to radiation through short-term treatment with ONC201. To understand how priming occurred, we performed RNA-Seq analysis and found that ONC201 suppressed the expression of cell cycle and DNA repair factors. In conclusion, we have shown that ONC201 can prime enhanced radiation response.
format	article
author	Francesca Amoroso Kimberley Glass Reema Singh Francisco Liberal Rebecca E. Steele Sarah Maguire Rohinton Tarapore Joshua E. Allen Sandra Van Schaeybroeck Karl T. Butterworth Kevin Prise Joe M. O’Sullivan Suneil Jain David J. Waugh Ian G. Mills
author_facet	Francesca Amoroso Kimberley Glass Reema Singh Francisco Liberal Rebecca E. Steele Sarah Maguire Rohinton Tarapore Joshua E. Allen Sandra Van Schaeybroeck Karl T. Butterworth Kevin Prise Joe M. O’Sullivan Suneil Jain David J. Waugh Ian G. Mills
author_sort	Francesca Amoroso
title	Modulating the unfolded protein response with ONC201 to impact on radiation response in prostate cancer cells
title_short	Modulating the unfolded protein response with ONC201 to impact on radiation response in prostate cancer cells
title_full	Modulating the unfolded protein response with ONC201 to impact on radiation response in prostate cancer cells
title_fullStr	Modulating the unfolded protein response with ONC201 to impact on radiation response in prostate cancer cells
title_full_unstemmed	Modulating the unfolded protein response with ONC201 to impact on radiation response in prostate cancer cells
title_sort	modulating the unfolded protein response with onc201 to impact on radiation response in prostate cancer cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e08cdcf6c9974257a805988e30144259
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Modulating the unfolded protein response with ONC201 to impact on radiation response in prostate cancer cells

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