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
Descripción
Sumario: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.

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