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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

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.citation	Proceedings of the National Academy of Sciences of the United States of America Vol. 109 Issue 22: pp. 8489-8494	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.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	journal article	es_ES
dc.identifier.doi	10.1073/pnas.1118349109	es_ES
dc.identifier.idgrec	085193	es_ES