RT Journal Article
T1 Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells
A1 Salazar Roa, María
A1 Carracedo, Arkaitz
A1 Salanueva, Iñigo
A1 Hernandez-Tiedra, Sonia
A1 Lorente, Mar
A1 Egia, Ainara
A1 Vazquez, Patricia
A1 Blazquez, Cristina
A1 Torres, Sofia
A1 Garcia, Stephane
A1 Nowak, Jonathan
A1 Fimia, Gian María
A1 Piacentini, Mauro
A1 Cecconi, Francesco
A1 Pandolfi, Pier Paola
A1 Gonzalez-Feria, Luis
A1 Iovanna, Juan
A1 Guzman, Manuel
A1 Boya, Patricia
A1 Velasco, Guillermo
AB 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.
PB American Society for Clinical Investigation
SN 0021-9738
YR 2009
FD 2009
LK https://hdl.handle.net/20.500.14352/95038
UL https://hdl.handle.net/20.500.14352/95038
LA eng
NO Salazar, 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.
NO This 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. 
NO Ministerio de Educación y Ciencia (España)
NO Comunidad de Madrid
NO Eusko Jaurlaritza
NO Universidad Complutense de Madrid
NO Canceropôle (France)
NO League against Cancer (France)
NO Federation of European Biochemical Societies
NO European Molecular Biology Organization
DS Docta Complutense
RD 8 abr 2025