Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in Glioblastoma

Autores
Slat, Emily A.; Sponagel, Jasmin; Marpegan, Luciano; Simon, Tatiana; Kfoury, Najla; Kim, Albert; Binz, Andrea; Herzog, Erik D.; Rubin, Joshua B.
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The safety and efficacy of chemotherapeutics can vary as a function of the time of their delivery during the day. This study aimed to improve the treatment of glioblastoma (GBM), the most common brain cancer, by testing whether the efficacy of the DNA alkylator temozolomide (TMZ) varies with the time of its administration. We found cell-intrinsic, daily rhythms in both human and mouse GBM cells. Circadian time of treatment affected TMZ sensitivity of murine GBM tumor cells in vitro. The maximum TMZ-induced DNA damage response, activation of apoptosis, and growth inhibition occurred near the daily peak in expression of the core clock gene Bmal1. Deletion of Bmal1 (Arntl) abolished circadian rhythms in gene expression and TMZ-induced activation of apoptosis and growth inhibition. These data indicate that tumor cell-intrinsic circadian rhythms are common to GBM tumors and can regulate TMZ cytotoxicity. Optimization of GBM treatment by timing TMZ administration to daily rhythms should be evaluated in prospective clinical trials.
Fil: Slat, Emily A.. Washington University in St. Louis; Estados Unidos
Fil: Sponagel, Jasmin. Washington University in St. Louis; Estados Unidos
Fil: Marpegan, Luciano. Washington University in St. Louis; Estados Unidos. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Simon, Tatiana. Washington University in St. Louis; Estados Unidos
Fil: Kfoury, Najla. Washington University in St. Louis; Estados Unidos
Fil: Kim, Albert. Washington University in St. Louis; Estados Unidos
Fil: Binz, Andrea. Washington University in St. Louis; Estados Unidos
Fil: Herzog, Erik D.. Washington University in St. Louis; Estados Unidos
Fil: Rubin, Joshua B.. Washington University in St. Louis; Estados Unidos
Materia
Bmal1 Gene
Dna Repair
Gbm
H2ax
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/42222
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/42222
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in GlioblastomaSlat, Emily A.Sponagel, JasminMarpegan, LucianoSimon, TatianaKfoury, NajlaKim, AlbertBinz, AndreaHerzog, Erik D.Rubin, Joshua B.Bmal1 GeneDna RepairGbmH2axhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The safety and efficacy of chemotherapeutics can vary as a function of the time of their delivery during the day. This study aimed to improve the treatment of glioblastoma (GBM), the most common brain cancer, by testing whether the efficacy of the DNA alkylator temozolomide (TMZ) varies with the time of its administration. We found cell-intrinsic, daily rhythms in both human and mouse GBM cells. Circadian time of treatment affected TMZ sensitivity of murine GBM tumor cells in vitro. The maximum TMZ-induced DNA damage response, activation of apoptosis, and growth inhibition occurred near the daily peak in expression of the core clock gene Bmal1. Deletion of Bmal1 (Arntl) abolished circadian rhythms in gene expression and TMZ-induced activation of apoptosis and growth inhibition. These data indicate that tumor cell-intrinsic circadian rhythms are common to GBM tumors and can regulate TMZ cytotoxicity. Optimization of GBM treatment by timing TMZ administration to daily rhythms should be evaluated in prospective clinical trials.Fil: Slat, Emily A.. Washington University in St. Louis; Estados UnidosFil: Sponagel, Jasmin. Washington University in St. Louis; Estados UnidosFil: Marpegan, Luciano. Washington University in St. Louis; Estados Unidos. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Simon, Tatiana. Washington University in St. Louis; Estados UnidosFil: Kfoury, Najla. Washington University in St. Louis; Estados UnidosFil: Kim, Albert. Washington University in St. Louis; Estados UnidosFil: Binz, Andrea. Washington University in St. Louis; Estados UnidosFil: Herzog, Erik D.. Washington University in St. Louis; Estados UnidosFil: Rubin, Joshua B.. Washington University in St. Louis; Estados UnidosSAGE Publications2017-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/42222Slat, Emily A.; Sponagel, Jasmin; Marpegan, Luciano; Simon, Tatiana; Kfoury, Najla; et al.; Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in Glioblastoma; SAGE Publications; Journal of Biological Rhythms; 32; 2; 3-2017; 121-1290748-7304CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1177/0748730417696788info:eu-repo/semantics/altIdentifier/url/http://journals.sagepub.com/doi/10.1177/0748730417696788info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:11:47Zoai:ri.conicet.gov.ar:11336/42222instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:11:47.829CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in Glioblastoma
title Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in Glioblastoma
spellingShingle Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in Glioblastoma
Slat, Emily A.
Bmal1 Gene
Dna Repair
Gbm
H2ax
title_short Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in Glioblastoma
title_full Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in Glioblastoma
title_fullStr Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in Glioblastoma
title_full_unstemmed Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in Glioblastoma
title_sort Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in Glioblastoma
dc.creator.none.fl_str_mv Slat, Emily A.
Sponagel, Jasmin
Marpegan, Luciano
Simon, Tatiana
Kfoury, Najla
Kim, Albert
Binz, Andrea
Herzog, Erik D.
Rubin, Joshua B.
author Slat, Emily A.
author_facet Slat, Emily A.
Sponagel, Jasmin
Marpegan, Luciano
Simon, Tatiana
Kfoury, Najla
Kim, Albert
Binz, Andrea
Herzog, Erik D.
Rubin, Joshua B.
author_role author
author2 Sponagel, Jasmin
Marpegan, Luciano
Simon, Tatiana
Kfoury, Najla
Kim, Albert
Binz, Andrea
Herzog, Erik D.
Rubin, Joshua B.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Bmal1 Gene
Dna Repair
Gbm
H2ax
topic Bmal1 Gene
Dna Repair
Gbm
H2ax
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The safety and efficacy of chemotherapeutics can vary as a function of the time of their delivery during the day. This study aimed to improve the treatment of glioblastoma (GBM), the most common brain cancer, by testing whether the efficacy of the DNA alkylator temozolomide (TMZ) varies with the time of its administration. We found cell-intrinsic, daily rhythms in both human and mouse GBM cells. Circadian time of treatment affected TMZ sensitivity of murine GBM tumor cells in vitro. The maximum TMZ-induced DNA damage response, activation of apoptosis, and growth inhibition occurred near the daily peak in expression of the core clock gene Bmal1. Deletion of Bmal1 (Arntl) abolished circadian rhythms in gene expression and TMZ-induced activation of apoptosis and growth inhibition. These data indicate that tumor cell-intrinsic circadian rhythms are common to GBM tumors and can regulate TMZ cytotoxicity. Optimization of GBM treatment by timing TMZ administration to daily rhythms should be evaluated in prospective clinical trials.
Fil: Slat, Emily A.. Washington University in St. Louis; Estados Unidos
Fil: Sponagel, Jasmin. Washington University in St. Louis; Estados Unidos
Fil: Marpegan, Luciano. Washington University in St. Louis; Estados Unidos. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Simon, Tatiana. Washington University in St. Louis; Estados Unidos
Fil: Kfoury, Najla. Washington University in St. Louis; Estados Unidos
Fil: Kim, Albert. Washington University in St. Louis; Estados Unidos
Fil: Binz, Andrea. Washington University in St. Louis; Estados Unidos
Fil: Herzog, Erik D.. Washington University in St. Louis; Estados Unidos
Fil: Rubin, Joshua B.. Washington University in St. Louis; Estados Unidos
description The safety and efficacy of chemotherapeutics can vary as a function of the time of their delivery during the day. This study aimed to improve the treatment of glioblastoma (GBM), the most common brain cancer, by testing whether the efficacy of the DNA alkylator temozolomide (TMZ) varies with the time of its administration. We found cell-intrinsic, daily rhythms in both human and mouse GBM cells. Circadian time of treatment affected TMZ sensitivity of murine GBM tumor cells in vitro. The maximum TMZ-induced DNA damage response, activation of apoptosis, and growth inhibition occurred near the daily peak in expression of the core clock gene Bmal1. Deletion of Bmal1 (Arntl) abolished circadian rhythms in gene expression and TMZ-induced activation of apoptosis and growth inhibition. These data indicate that tumor cell-intrinsic circadian rhythms are common to GBM tumors and can regulate TMZ cytotoxicity. Optimization of GBM treatment by timing TMZ administration to daily rhythms should be evaluated in prospective clinical trials.
publishDate 2017
dc.date.none.fl_str_mv 2017-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/42222
Slat, Emily A.; Sponagel, Jasmin; Marpegan, Luciano; Simon, Tatiana; Kfoury, Najla; et al.; Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in Glioblastoma; SAGE Publications; Journal of Biological Rhythms; 32; 2; 3-2017; 121-129
0748-7304
CONICET Digital
CONICET
url http://hdl.handle.net/11336/42222
identifier_str_mv Slat, Emily A.; Sponagel, Jasmin; Marpegan, Luciano; Simon, Tatiana; Kfoury, Najla; et al.; Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in Glioblastoma; SAGE Publications; Journal of Biological Rhythms; 32; 2; 3-2017; 121-129
0748-7304
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1177/0748730417696788
info:eu-repo/semantics/altIdentifier/url/http://journals.sagepub.com/doi/10.1177/0748730417696788
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv SAGE Publications
publisher.none.fl_str_mv SAGE Publications
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844614020189913088
score 13.070432

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