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Normalization of sphingomyelin levels by 2-hydroxyoleic acid induces autophagic cell death of SF767 cancer cells

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Normalization of sphingomyelin levels by 2-hydroxyoleic acid induces autophagic cell death of SF767 cancer cells

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, M. 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	Autophagy Vol. 8 Issue 10: pp. 1542-1544	es_ES
dc.identifier.uri	http://hdl.handle.net/10550/44560
dc.description.abstract	The very high mortality rate of gliomas reflects the unmet therapeutic need associated with this type of brain tumor. We have discovered that the plasma membrane fulfills a critical role in the propagation of tumorigenic signals, whereby changes in membrane lipid content can either activate or silence relevant pathways. We have designed a synthetic fatty acid, 2-hydroxyoleic acid (2OHOA), that specifically activates sphingomyelin synthase (SGMS), thereby modifying the lipid content of cancer cell membranes and restoring lipid levels to those found in normal cells. In reverting, the structure of the membrane by activating SGMS, 2OHOA inhibits the RAS-MAPK pathway, which in turn fails to activate the CCND (Cyclin D)-CDK4/CDK6 and PI3K-AKT1 pathways. The overall result in SF767 cancer cells, a line that is resistant to apoptosis, is the sequential induction of cell cycle arrest, cell differentiation and autophagy. Such effects are not observed in normal cells (MRC-5) and thus, this specific activation of programmed cell death infers greater efficacy and lower toxicity to 2OHOA than that associated with temozolomide (TMZ), the reference drug for the treatment of glioma.	es_ES
dc.subject	minerval	es_ES
dc.subject	cancer	es_ES
dc.subject	cell membrane	es_ES
dc.subject	signaling	es_ES
dc.subject	lipid bilayer and proliferation	es_ES
dc.subject	phospholipid	es_ES
dc.title	Normalization of sphingomyelin levels by 2-hydroxyoleic acid induces autophagic cell death of SF767 cancer cells	es_ES
dc.type	journal article	es_ES
dc.identifier.doi	10.4161/auto.21341	es_ES
dc.identifier.idgrec	085196	es_ES