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Dihydroceramide accumulation mediates cytotoxic autophagy of cancer cells via autolysosome destabilization

Hernandez-Tiedra, Sonia, Fabrias, Gemma, Davila, David, Salanueva, Inigo J, Casas, Josefina, Montes, L Ruth, Anton, Zurine, Garcia-Taboada, Elena, Salazar-Roa, Maria, Lorente, Mar, Nylandsted, Jesper, Armstrong, Jane, Lopez-Valero, Israel, McKee, Christopher, Serrano-Puebla, Ana, Garcia-Lopez, Roberto, Gonzalez-Martinez, Jose, Abad, Jose L, Hanada, Kentaro, Boya, Patricia, Goni, Felix M, Guzman, Manuel, Lovat, Penny, Jaattela, Marja, Alonso, Alicia and Velasco, Guillermo (2016) Dihydroceramide accumulation mediates cytotoxic autophagy of cancer cells via autolysosome destabilization. Autophagy, 12 (11). pp. 2213-2229. ISSN 1554-8627

Item Type: Article


Autophagy is considered primarily a cell survival process, although it can also lead to cell death. However, the factors that dictate the shift between these 2 opposite outcomes remain largely unknown. In this work, we used Δ9-tetrahydrocannabinol (THC, the main active component of marijuana, a compound that triggers autophagy-mediated cancer cell death) and nutrient deprivation (an autophagic stimulus that triggers cytoprotective autophagy) to investigate the precise molecular mechanisms responsible for the activation of cytotoxic autophagy in cancer cells. By using a wide array of experimental approaches we show that THC (but not nutrient deprivation) increases the dihydroceramide:ceramide ratio in the endoplasmic reticulum of glioma cells, and this alteration is directed to autophagosomes and autolysosomes to promote lysosomal membrane permeabilization, cathepsin release and the subsequent activation of apoptotic cell death. These findings pave the way to clarify the regulatory mechanisms that determine the selective activation of autophagy-mediated cancer cell death.

Hernandez Tiedra et al revV4_final version for publication.pdf - Accepted Version
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Depositing User: Jane Armstrong


Item ID: 6544
Identification Number:
ISSN: 1554-8627
Official URL:

Users with ORCIDS

ORCID for Jane Armstrong: ORCID iD

Catalogue record

Date Deposited: 23 Sep 2016 14:23
Last Modified: 04 Feb 2020 11:27


Author: Jane Armstrong ORCID iD
Author: Sonia Hernandez-Tiedra
Author: Gemma Fabrias
Author: David Davila
Author: Inigo J Salanueva
Author: Josefina Casas
Author: L Ruth Montes
Author: Zurine Anton
Author: Elena Garcia-Taboada
Author: Maria Salazar-Roa
Author: Mar Lorente
Author: Jesper Nylandsted
Author: Israel Lopez-Valero
Author: Christopher McKee
Author: Ana Serrano-Puebla
Author: Roberto Garcia-Lopez
Author: Jose Gonzalez-Martinez
Author: Jose L Abad
Author: Kentaro Hanada
Author: Patricia Boya
Author: Felix M Goni
Author: Manuel Guzman
Author: Penny Lovat
Author: Marja Jaattela
Author: Alicia Alonso
Author: Guillermo Velasco

University Divisions

Faculty of Health Sciences and Wellbeing
Faculty of Health Sciences and Wellbeing > School of Nursing and Health Sciences


Sciences > Biomedical Sciences

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