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Título

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

AutorSalazar, María; Carracedo, Arkaitz; Salanueva, Íñigo J.; Hernández-Tiedra, Sonia; Lorente, Mar; Egia, Ainara; Vázquez Pérez, Patricia ; Blázquez, Cristina; Torres, Sofía ; García, Stéphane; Nowak, Jonathan; Fimia, Gian María; Piacentini, Mauro; Cecconi, Francesco; Pandolfi, Pier Paolo; González-Feria, Luis; Iovanna, Juan Lucio; Guzmán, Manuel; Boya, Patricia ; Velasco, Guillermo
Palabras claveCancer cells
Human glioma cell death
Cannabinoids
Antitumor action
Autophagy
Δ9-Tetrahydrocannabinol (THC)
Marijuana
Fecha de publicación1-abr-2009
EditorAmerican Society for Clinical Investigation
CitaciónThe Journal of Clinical Investigation 119(5):1359–1372(2009)
ResumenAutophagy 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.
Descripción14 pages, 8 figures.
Versión del editorhttp://dx.doi.org/10.1172/JCI37948
URIhttp://hdl.handle.net/10261/12085
DOI10.1172/JCI37948
ISSN0021-9738
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