2-Hydroxyoleate, a nontoxic membrane binding anticancer drug, induces glioma cell differentiation and autophagy
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2-Hydroxyoleate, a nontoxic membrane binding anticancer drug, induces glioma cell differentiation and autophagy

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2-Hydroxyoleate, a nontoxic membrane binding anticancer drug, induces glioma cell differentiation and autophagy

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dc.contributor.author Terés, Silvia es_ES
dc.contributor.author Lladó, Victoria es_ES
dc.contributor.author Higuera, Mónica es_ES
dc.contributor.author Barceló-Coblijn, Gwendolyn es_ES
dc.contributor.author Martin, Maria Laura es_ES
dc.contributor.author Noguera-Salvà, Maria Antònia es_ES
dc.contributor.author Marcilla-Etxenike, Amaia es_ES
dc.contributor.author García Verdugo, José Manuel es_ES
dc.contributor.author Soriano-Navarro, Mario es_ES
dc.contributor.author Saus Ortega, Carles es_ES
dc.contributor.author Gómez-Pinedo, Ulises es_ES
dc.contributor.author Busquets, Xavier es_ES
dc.contributor.author Escribá, Pablo V. es_ES
dc.date.accessioned 2015-06-19T10:19:54Z
dc.date.available 2015-06-19T10:19:54Z
dc.date.issued 2012 es_ES
dc.identifier.uri http://hdl.handle.net/10550/44559
dc.description.abstract Despite recent advances in the development of new cancer therapies, the treatment options for glioma remain limited, and the survival rate of patients has changed little over the past three decades. Here, we show that 2-hydroxyoleic acid (2OHOA) induces differentiation and autophagy of human glioma cells. Compared to the current reference drug for this condition, temozolomide (TMZ), 2OHOA combated glioma more efficiently and, unlike TMZ, tumor relapse was not observed following 2OHOA treatment. The novel mechanism of action of 2OHOA is associated with important changes in membrane-lipid composition, primarily a recovery of sphingomyelin (SM) levels, which is markedly low in glioma cells before treatment. Parallel to membrane-lipid regulation, treatment with 2OHOA induced a dramatic translocation of Ras from the membrane to the cytoplasm, which inhibited the MAP kinase pathway, reduced activity of the PI3K/Akt pathway, and downregulated Cyclin D-CDK4/6 proteins followed by hypophosphorylation of the retinoblastoma protein (RB). These regulatory effects were associated with induction of glioma cell differentiation into mature glial cells followed by autophagic cell death. Given its high efficacy, low toxicity, ease of oral administration, and good distribution to the brain, 2OHOA constitutes a new and potentially valuable therapeutic tool for glioma patients. es_ES
dc.source Proceedings of the National Academy of Sciences of the United States of America Vol. 109 Issue 22: pp. 8489-8494 es_ES
dc.subject fatty acids es_ES
dc.subject sphingomyelin synthase es_ES
dc.subject cancer drug target es_ES
dc.subject glioma biomarker es_ES
dc.title 2-Hydroxyoleate, a nontoxic membrane binding anticancer drug, induces glioma cell differentiation and autophagy es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.identifier.doi 10.1073/pnas.1118349109 es_ES
dc.identifier.idgrec 085193 es_ES

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