Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells

Salazar Roa, María; Carracedo, Arkaitz; Salanueva, Iñigo; Hernandez-Tiedra, Sonia; Lorente, Mar; Egia, Ainara; Vazquez, Patricia; Blazquez, Cristina; Torres, Sofia; Garcia, Stephane; Nowak, Jonathan; Fimia, Gian María; Piacentini, Mauro; Cecconi, Francesco; Pandolfi, Pier Paola; Gonzalez-Feria, Luis; Iovanna, Juan; Guzman, Manuel; Boya, Patricia; Velasco, Guillermo

Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells

Autophagy can promote cell survival or cell death, but the molecular basis underlying its dual role in cancer remains obscure. Here we demonstrate that Δ9-tetrahydrocannabinol (THC), the main active component of marijuana, induces human glioma cell death through stimulation of autophagy. Our data in...

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Detalles Bibliográficos
Autores:	Salazar Roa, María, Carracedo, Arkaitz, Salanueva, Iñigo, Hernandez-Tiedra, Sonia, Lorente, Mar, Egia, Ainara, Vazquez, Patricia, Blazquez, Cristina, Torres, Sofia, Garcia, Stephane, Nowak, Jonathan, Fimia, Gian María, Piacentini, Mauro, Cecconi, Francesco, Pandolfi, Pier Paola, Gonzalez-Feria, Luis, Iovanna, Juan, Guzman, Manuel, Boya, Patricia, Velasco, Guillermo
Tipo de recurso:	artículo
Fecha de publicación:	2009
País:	España
Institución:	Universidad Complutense de Madrid (UCM)
Repositorio:	Docta Complutense
Idioma:	inglés
OAI Identifier:	oai:docta.ucm.es:20.500.14352/95038
Acceso en línea:	https://hdl.handle.net/20.500.14352/95038
Access Level:	acceso abierto
Palabra clave:	576.353 616. 831-006. 484 577.175.82 Cancer Gliomas AKt-mTOR axis Tribbles Autophagy Cannabinoids Biología molecular (Biología) Bioquímica (Biología) Oncología 2403 Bioquímica 2407 Biología Celular 2415 Biología Molecular 3201.01 Oncología

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oai_identifier_str	oai:docta.ucm.es:20.500.14352/95038
network_acronym_str	ES
network_name_str	España
repository_id_str
spelling	Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cellsSalazar Roa, MaríaCarracedo, ArkaitzSalanueva, IñigoHernandez-Tiedra, SoniaLorente, MarEgia, AinaraVazquez, PatriciaBlazquez, CristinaTorres, SofiaGarcia, StephaneNowak, JonathanFimia, Gian MaríaPiacentini, MauroCecconi, FrancescoPandolfi, Pier PaolaGonzalez-Feria, LuisIovanna, JuanGuzman, ManuelBoya, PatriciaVelasco, Guillermo576.353616. 831-006. 484577.175.82CancerGliomasAKt-mTOR axisTribblesAutophagyCannabinoidsBiología molecular (Biología)Bioquímica (Biología)Oncología2403 Bioquímica2407 Biología Celular2415 Biología Molecular3201.01 OncologíaAutophagy can promote cell survival or cell death, but the molecular basis underlying its dual role in cancer remains obscure. Here we demonstrate that Δ9-tetrahydrocannabinol (THC), the main active component of marijuana, induces human glioma cell death through stimulation of autophagy. Our data indicate that THC induced ceramide accumulation and eukaryotic translation initiation factor 2α (eIF2α) phosphorylation and thereby activated an ER stress response that promoted autophagy via tribbles homolog 3–dependent (TRB3-dependent) inhibition of the Akt/mammalian target of rapamycin complex 1 (mTORC1) axis. We also showed that autophagy is upstream of apoptosis in cannabinoid-induced human and mouse cancer cell death and that activation of this pathway was necessary for the antitumor action of cannabinoids in vivo. These findings describe a mechanism by which THC can promote the autophagic death of human and mouse cancer cells and provide evidence that cannabinoid administration may be an effective therapeutic strategy for targeting human cancers.American Society for Clinical InvestigationUniversidad Complutense de Madrid20092009-01-0120092009-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/95038reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/950382026-06-02T12:44:21Z
dc.title.none.fl_str_mv	Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells
title	Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells
spellingShingle	Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells Salazar Roa, María 576.353 616. 831-006. 484 577.175.82 Cancer Gliomas AKt-mTOR axis Tribbles Autophagy Cannabinoids Biología molecular (Biología) Bioquímica (Biología) Oncología 2403 Bioquímica 2407 Biología Celular 2415 Biología Molecular 3201.01 Oncología
title_short	Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells
title_full	Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells
title_fullStr	Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells
title_full_unstemmed	Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells
title_sort	Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells
dc.creator.none.fl_str_mv	Salazar Roa, María Carracedo, Arkaitz Salanueva, Iñigo Hernandez-Tiedra, Sonia Lorente, Mar Egia, Ainara Vazquez, Patricia Blazquez, Cristina Torres, Sofia Garcia, Stephane Nowak, Jonathan Fimia, Gian María Piacentini, Mauro Cecconi, Francesco Pandolfi, Pier Paola Gonzalez-Feria, Luis Iovanna, Juan Guzman, Manuel Boya, Patricia Velasco, Guillermo
author	Salazar Roa, María
author_facet	Salazar Roa, María Carracedo, Arkaitz Salanueva, Iñigo Hernandez-Tiedra, Sonia Lorente, Mar Egia, Ainara Vazquez, Patricia Blazquez, Cristina Torres, Sofia Garcia, Stephane Nowak, Jonathan Fimia, Gian María Piacentini, Mauro Cecconi, Francesco Pandolfi, Pier Paola Gonzalez-Feria, Luis Iovanna, Juan Guzman, Manuel Boya, Patricia Velasco, Guillermo
author_role	author
author2	Carracedo, Arkaitz Salanueva, Iñigo Hernandez-Tiedra, Sonia Lorente, Mar Egia, Ainara Vazquez, Patricia Blazquez, Cristina Torres, Sofia Garcia, Stephane Nowak, Jonathan Fimia, Gian María Piacentini, Mauro Cecconi, Francesco Pandolfi, Pier Paola Gonzalez-Feria, Luis Iovanna, Juan Guzman, Manuel Boya, Patricia Velasco, Guillermo
author2_role	author author author author author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Universidad Complutense de Madrid
dc.subject.none.fl_str_mv	576.353 616. 831-006. 484 577.175.82 Cancer Gliomas AKt-mTOR axis Tribbles Autophagy Cannabinoids Biología molecular (Biología) Bioquímica (Biología) Oncología 2403 Bioquímica 2407 Biología Celular 2415 Biología Molecular 3201.01 Oncología
topic	576.353 616. 831-006. 484 577.175.82 Cancer Gliomas AKt-mTOR axis Tribbles Autophagy Cannabinoids Biología molecular (Biología) Bioquímica (Biología) Oncología 2403 Bioquímica 2407 Biología Celular 2415 Biología Molecular 3201.01 Oncología
description	Autophagy can promote cell survival or cell death, but the molecular basis underlying its dual role in cancer remains obscure. Here we demonstrate that Δ9-tetrahydrocannabinol (THC), the main active component of marijuana, induces human glioma cell death through stimulation of autophagy. Our data indicate that THC induced ceramide accumulation and eukaryotic translation initiation factor 2α (eIF2α) phosphorylation and thereby activated an ER stress response that promoted autophagy via tribbles homolog 3–dependent (TRB3-dependent) inhibition of the Akt/mammalian target of rapamycin complex 1 (mTORC1) axis. We also showed that autophagy is upstream of apoptosis in cannabinoid-induced human and mouse cancer cell death and that activation of this pathway was necessary for the antitumor action of cannabinoids in vivo. These findings describe a mechanism by which THC can promote the autophagic death of human and mouse cancer cells and provide evidence that cannabinoid administration may be an effective therapeutic strategy for targeting human cancers.
publishDate	2009
dc.date.none.fl_str_mv	2009 2009-01-01 2009 2009-01-01
dc.type.none.fl_str_mv	journal article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://hdl.handle.net/20.500.14352/95038
url	https://hdl.handle.net/20.500.14352/95038
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	American Society for Clinical Investigation
publisher.none.fl_str_mv	American Society for Clinical Investigation
dc.source.none.fl_str_mv	reponame:Docta Complutense instname:Universidad Complutense de Madrid (UCM)
instname_str	Universidad Complutense de Madrid (UCM)
reponame_str	Docta Complutense
collection	Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_	1869406645449129984
score	15,81155

Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells

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