Aviso: para depositar documentos, por favor, inicia sesión e identifícate con tu cuenta de correo institucional de la UCM con el botón MI CUENTA UCM. No emplees la opción AUTENTICACIÓN CON CONTRASEÑA
 

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

dc.contributor.authorSalazar Roa, María
dc.contributor.authorCarracedo, Arkaitz
dc.contributor.authorSalanueva, Iñigo
dc.contributor.authorHernandez-Tiedra, Sonia
dc.contributor.authorLorente, Mar
dc.contributor.authorEgia, Ainara
dc.contributor.authorVazquez, Patricia
dc.contributor.authorBlazquez, Cristina
dc.contributor.authorTorres, Sofia
dc.contributor.authorGarcia, Stephane
dc.contributor.authorNowak, Jonathan
dc.contributor.authorFimia, Gian María
dc.contributor.authorPiacentini, Mauro
dc.contributor.authorCecconi, Francesco
dc.contributor.authorPandolfi, Pier Paola
dc.contributor.authorGonzalez-Feria, Luis
dc.contributor.authorIovanna, Juan
dc.contributor.authorGuzman, Manuel
dc.contributor.authorBoya, Patricia
dc.contributor.authorVelasco, Guillermo
dc.date.accessioned2024-01-24T11:09:32Z
dc.date.available2024-01-24T11:09:32Z
dc.date.issued2009
dc.descriptionThis work was supported by grants from the Spanish Ministry of Education and Science (MEC) (HF2005/0021, to G. Velasco; SAF2006/00918, to M. Guzmán; and BFU2006-00508, to P. Boya), Santander-Complutense PR34/07-15856, to G. Velasco), Comunidad de Madrid (S-SAL/0261/2006, to M. Guzmán), and La Ligue contre le Cancer and Canceropole PACA (to J.L. Iovanna). M. Salazar was the recipient of a fellowship from the MEC. A. Carracedo was the recipient of fellowships from Gobierno Vasco, the Federation of European Biochemical Societies, and the European Molecular Biology Organization. M. Lorente and P. Boya have a Juan de la Cierva and a Ramón y Cajal contract from the MEC, respectively. S. Hernández-Tiedra has a technician contract from the Spanish Ministry of Education and the Fondo Social Europeo.
dc.description.abstractAutophagy 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.
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Ciencias Biológicas
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Educación y Ciencia (España)
dc.description.sponsorshipComunidad de Madrid
dc.description.sponsorshipEusko Jaurlaritza
dc.description.sponsorshipUniversidad Complutense de Madrid
dc.description.sponsorshipCanceropôle (France)
dc.description.sponsorshipLeague against Cancer (France)
dc.description.sponsorshipFederation of European Biochemical Societies
dc.description.sponsorshipEuropean Molecular Biology Organization
dc.description.statuspub
dc.identifier.citationSalazar, María, et al. «Cannabinoid Action Induces Autophagy-Mediated Cell Death through Stimulation of ER Stress in Human Glioma Cells». Journal of Clinical Investigation, vol. 119, n.o 5, mayo de 2009, pp. 1359-72. https://doi.org/10.1172/JCI37948.
dc.identifier.doi10.1172/JCI37948
dc.identifier.essn1558-8238
dc.identifier.issn0021-9738
dc.identifier.officialurlhttps://doi.org/10.1172/JCI37948
dc.identifier.urihttps://hdl.handle.net/20.500.14352/95038
dc.issue.number5
dc.journal.titleThe Journal of Clinical Investigation
dc.language.isoeng
dc.page.final1372
dc.page.initial1359
dc.publisherAmerican Society for Clinical Investigation
dc.rights.accessRightsopen access
dc.subject.cdu576.353
dc.subject.cdu616. 831-006. 484
dc.subject.cdu577.175.82
dc.subject.keywordCancer
dc.subject.keywordGliomas
dc.subject.keywordAKt-mTOR axis
dc.subject.keywordTribbles
dc.subject.keywordAutophagy
dc.subject.keywordCannabinoids
dc.subject.ucmBiología molecular (Biología)
dc.subject.ucmBioquímica (Biología)
dc.subject.ucmOncología
dc.subject.unesco2403 Bioquímica
dc.subject.unesco2407 Biología Celular
dc.subject.unesco2415 Biología Molecular
dc.subject.unesco3201.01 Oncología
dc.titleCannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number119
dspace.entity.typePublication
relation.isAuthorOfPublication85418c2e-51eb-43c9-a82f-05a96903381f
relation.isAuthorOfPublication.latestForDiscovery85418c2e-51eb-43c9-a82f-05a96903381f

Download

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Cannabinoid_action.pdf
Size:
10.04 MB
Format:
Adobe Portable Document Format

Collections