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

Salazar‐Roa, María; Carracedo, Arkaitz; Salanueva, Íñigo J.; Hernández‐Tiedra, Sonia; Lorente, Mar; Egia, Ainara; Vázquez, Patricia; Blázquez, Cristina; Torres, Sofía; Garcia, Stéphane; Nowak, Jonathan A.; Fimia, Gian María; Piacentini, Mauro; Cecconi, Francesco; Pandolfi, Pier Paolo; González‐Feria, Luis; Iovanna, Juan; Guzmán, Manuel; Boya, Patricia; Velasco, Guillermo

doi:10.1172/jci37948

articleJournal of Clinical InvestigationMar 26, 2009BRONZE OA

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

MSMaría Salazar‐Roa ACArkaitz Carracedo ÍJÍñigo J. Salanueva SHSonia Hernández‐Tiedra MLMar Lorente

Universidad Complutense de Madrid · Harvard University Press · +6 more institutions

PubMed

Indexed incrossrefdoajpubmed

Abstract

Autophagy can promote cell survival or cell death, but the molecular basis underlying its dual role in cancer remains obscure. Here we demonstrate that delta(9)-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 2alpha (eIF2alpha) 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…

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Topics & keywords

Topics

Keywords

Autophagy
mTORC1
Programmed cell death
Cell biology
Apoptosis
PI3K/AKT/mTOR pathway
Biology
Integrated stress response

UN Sustainable Development Goals

Good health and well-being

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