Inactivation of chromatin remodeling factors sensitizes cells to selective cytotoxic stress

Miles D Freeman, Tryphon Mazu, Jana S Miles, Selina Darling-Reed, Hernan Flores-Rozas College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, USA Abstract: The SWI/SNF chromatin-remodeling complex plays an essential role in several cellular processes inclu...

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Autores principales:	Freeman MD, Mazu T, Miles JS, Darling-Reed S, Flores-Rozas H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/2417c6b0aa0140e28abde2dd72d8e9ed
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spelling	oai:doaj.org-article:2417c6b0aa0140e28abde2dd72d8e9ed2021-12-02T00:32:57ZInactivation of chromatin remodeling factors sensitizes cells to selective cytotoxic stress1177-5491https://doaj.org/article/2417c6b0aa0140e28abde2dd72d8e9ed2014-11-01T00:00:00Zhttp://www.dovepress.com/inactivation-of-chromatin-remodeling-factors-sensitizes-cells-to-selec-peer-reviewed-article-BTThttps://doaj.org/toc/1177-5491 Miles D Freeman, Tryphon Mazu, Jana S Miles, Selina Darling-Reed, Hernan Flores-Rozas College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, USA Abstract: The SWI/SNF chromatin-remodeling complex plays an essential role in several cellular processes including cell proliferation, differentiation, and DNA repair. Loss of normal function of the SWI/SNF complex because of mutations in its subunits correlates with tumorigenesis in humans. For many of these cancers, cytotoxic chemotherapy is the primary, and sometimes the only, therapeutic alternative. Among the antineoplastic agents, anthracyclines are a common treatment option. Although effective, resistance to these agents usually develops and serious dose-related toxicity, namely, chronic cardiotoxicity, limits its use. Previous work from our laboratory showed that a deletion of the SWI/SNF factor SNF2 resulted in hypersensitivity to doxorubicin. We further investigated the contribution of other chromatin remodeling complex components in the response to cytotoxic chemotherapy. Our results indicate that, of the eight SWI/SNF strains tested, snf2, taf14, and swi3 were the most sensitive and displayed distinct sensitivity to different cytotoxic agents, while snf5 displayed resistance. Our experimental results indicate that the SWI/SNF complex plays a critical role in protecting cells from exposure to cytotoxic chemotherapy and other cytotoxic agents. Our findings may prove useful in the development of a strategy aimed at targeting these genes to provide an alternative by hypersensitizing cancer cells to chemotherapeutic agents. Keywords: chromatin remodeling, cancer, DNA damage/repair, heat-shock response, oxidative stressFreeman MDMazu TMiles JSDarling-Reed SFlores-Rozas HDove Medical PressarticleMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol 2014, Iss default, Pp 269-280 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Freeman MD Mazu T Miles JS Darling-Reed S Flores-Rozas H Inactivation of chromatin remodeling factors sensitizes cells to selective cytotoxic stress
description	Miles D Freeman, Tryphon Mazu, Jana S Miles, Selina Darling-Reed, Hernan Flores-Rozas College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, USA Abstract: The SWI/SNF chromatin-remodeling complex plays an essential role in several cellular processes including cell proliferation, differentiation, and DNA repair. Loss of normal function of the SWI/SNF complex because of mutations in its subunits correlates with tumorigenesis in humans. For many of these cancers, cytotoxic chemotherapy is the primary, and sometimes the only, therapeutic alternative. Among the antineoplastic agents, anthracyclines are a common treatment option. Although effective, resistance to these agents usually develops and serious dose-related toxicity, namely, chronic cardiotoxicity, limits its use. Previous work from our laboratory showed that a deletion of the SWI/SNF factor SNF2 resulted in hypersensitivity to doxorubicin. We further investigated the contribution of other chromatin remodeling complex components in the response to cytotoxic chemotherapy. Our results indicate that, of the eight SWI/SNF strains tested, snf2, taf14, and swi3 were the most sensitive and displayed distinct sensitivity to different cytotoxic agents, while snf5 displayed resistance. Our experimental results indicate that the SWI/SNF complex plays a critical role in protecting cells from exposure to cytotoxic chemotherapy and other cytotoxic agents. Our findings may prove useful in the development of a strategy aimed at targeting these genes to provide an alternative by hypersensitizing cancer cells to chemotherapeutic agents. Keywords: chromatin remodeling, cancer, DNA damage/repair, heat-shock response, oxidative stress
format	article
author	Freeman MD Mazu T Miles JS Darling-Reed S Flores-Rozas H
author_facet	Freeman MD Mazu T Miles JS Darling-Reed S Flores-Rozas H
author_sort	Freeman MD
title	Inactivation of chromatin remodeling factors sensitizes cells to selective cytotoxic stress
title_short	Inactivation of chromatin remodeling factors sensitizes cells to selective cytotoxic stress
title_full	Inactivation of chromatin remodeling factors sensitizes cells to selective cytotoxic stress
title_fullStr	Inactivation of chromatin remodeling factors sensitizes cells to selective cytotoxic stress
title_full_unstemmed	Inactivation of chromatin remodeling factors sensitizes cells to selective cytotoxic stress
title_sort	inactivation of chromatin remodeling factors sensitizes cells to selective cytotoxic stress
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/2417c6b0aa0140e28abde2dd72d8e9ed
work_keys_str_mv	AT freemanmd inactivationofchromatinremodelingfactorssensitizescellstoselectivecytotoxicstress AT mazut inactivationofchromatinremodelingfactorssensitizescellstoselectivecytotoxicstress AT milesjs inactivationofchromatinremodelingfactorssensitizescellstoselectivecytotoxicstress AT darlingreeds inactivationofchromatinremodelingfactorssensitizescellstoselectivecytotoxicstress AT floresrozash inactivationofchromatinremodelingfactorssensitizescellstoselectivecytotoxicstress
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Inactivation of chromatin remodeling factors sensitizes cells to selective cytotoxic stress

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