Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells<\/strong><\/p>\nMar\u00eda Salazar1,2, Arkaitz Carracedo1, \u00cd\u00f1igo J. Salanueva1, Sonia Hern\u00e1ndez-Tiedra1, Mar Lorente1,2, Ainara Egia1, Patricia V\u00e1zquez3, Cristina Bl\u00e1zquez1,2, Sof\u00eda Torres1, Stephane Garc\u00eda4, Jonathan Nowak4, Gian Mar\u00eda Fimia5, Mauro Piacentini5, Francesco Cecconi6, Pier Paolo Pandolfi7, Luis Gonz\u00e1lez-Feria8, Juan L. Iovanna4, Manuel Guzm\u00e1n1,2, Patricia Boya3 and Guillermo Velasco1,2<\/p>\n
1 Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.<\/p>\n
2 Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.<\/p>\n
3 3D Lab (Development, Differentiation, and Degeneration), Department of Cellular and Molecular Physiopathology, Centro de Investigaciones Biol\u00f3gicas, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Madrid, Spain.<\/p>\n
4 INSERM U624, Campus de Luminy, Marseille, France.<\/p>\n
5 National Institute for Infectious Diseases, IRCCS \u201cL. Spallanzani,\u201d Rome, Italy.<\/p>\n
6 Laboratory of Molecular Neuroembryology, IRCCS Fondazione Santa Lucia and Department of Biology, University of Rome \u201cTor Vergata,\u201d Rome, Italy.<\/p>\n
7 Cancer Genetics Program, Beth Israel Deaconess Cancer Center and Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.<\/p>\n
8 Department of Neurosurgery, University Hospital, Tenerife, Spain.<\/p>\n
Address correspondence to: Guillermo Velasco, Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, c\/ Jos\u00e9 Antonio Novais s\/n, 28040 Madrid, Spain. Phone: 34-913944668; Fax: 34-913944672; E-mail:gvd@bbm1.ucm.es<\/strong>.<\/p>\nFirst published April 1, 2009<\/strong><\/p>\n– 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 \u03949-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 2\u03b1 (eIF2\u03b1) phosphorylation and thereby activated an ER stress response that promoted autophagy via tribbles homolog 3\u2013dependent (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.<\/strong>]].<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[32],"tags":[],"_links":{"self":[{"href":"https:\/\/marina.swarpeca.es\/revista\/wp-json\/wp\/v2\/posts\/736"}],"collection":[{"href":"https:\/\/marina.swarpeca.es\/revista\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/marina.swarpeca.es\/revista\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/marina.swarpeca.es\/revista\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/marina.swarpeca.es\/revista\/wp-json\/wp\/v2\/comments?post=736"}],"version-history":[{"count":0,"href":"https:\/\/marina.swarpeca.es\/revista\/wp-json\/wp\/v2\/posts\/736\/revisions"}],"wp:attachment":[{"href":"https:\/\/marina.swarpeca.es\/revista\/wp-json\/wp\/v2\/media?parent=736"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/marina.swarpeca.es\/revista\/wp-json\/wp\/v2\/categories?post=736"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/marina.swarpeca.es\/revista\/wp-json\/wp\/v2\/tags?post=736"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}