2-Hydroxyoleic acid induces ER stress and autophagy in various human glioma cell lines.

<h4>Background</h4>2-Hydroxyoleic acid is a synthetic fatty acid with potent anti-cancer activity which does not induce undesired side effects. However, the molecular and cellular mechanisms by which this compound selectively kills human glioma cancer cells without killing normal cells i...

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Autores principales:	Amaia Marcilla-Etxenike, Maria Laura Martín, Maria Antònia Noguera-Salvà, José Manuel García-Verdugo, Mario Soriano-Navarro, Indranil Dey, Pablo V Escribá, Xavier Busquets
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d0a2a546870b47b49d5a2e2429a3d008
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spelling	oai:doaj.org-article:d0a2a546870b47b49d5a2e2429a3d0082021-11-18T08:10:56Z2-Hydroxyoleic acid induces ER stress and autophagy in various human glioma cell lines.1932-620310.1371/journal.pone.0048235https://doaj.org/article/d0a2a546870b47b49d5a2e2429a3d0082012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23133576/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>2-Hydroxyoleic acid is a synthetic fatty acid with potent anti-cancer activity which does not induce undesired side effects. However, the molecular and cellular mechanisms by which this compound selectively kills human glioma cancer cells without killing normal cells is not fully understood. The present study was designed to determine the molecular bases underlying the potency against 1321N1, SF-767 and U118 human glioma cell lines growth without affecting non cancer MRC-5 cells.<h4>Methodology/principal findings</h4>The cellular levels of endoplasmic reticulum (ER) stress, unfolded protein response (UPR) and autophagy markers were determined by quantitative RT-PCR and immunoblotting on 1321N1, SF-767 and U118 human glioma cells and non-tumor MRC-5 cells incubated in the presence or absence of 2OHOA or the ER stress/autophagy inducer, palmitate. The cellular response to these agents was evaluated by fluorescence microscopy, electron microscopy and flow cytometry. We have observed that 2OHOA treatments induced augments in the expression of important ER stress/UPR markers, such as phosphorylated eIF2α, IRE1α, CHOP, ATF4 and the spliced form of XBP1 in human glioma cells. Concomitantly, 2OHOA led to the arrest of 1321N1 cells in the G(2)/M phase of the cell cycle, with down-regulation of cyclin B1 and Cdk1/Cdc2 proteins in the three glioma cell lines studied. Finally, 2OHOA induced autophagy in 1321N1, SF-767 and U118 cells, with the appearance of autophagic vesicles and the up-regulation of LC3BI, LC3BII and ATG7 in 1321N1 cells, increases of LC3BI, LC3BII and ATG5 in SF-767 cells and up-regulation of LC3BI and LC3BII in U118 cells. Importantly, 2OHOA failed to induce such changes in non-tumor MRC-5 cells.<h4>Conclusion/significance</h4>The present results demonstrate that 2OHOA induces ER stress/UPR and autophagy in human glioma (1321N1, SF-767 and U118 cell lines) but not normal (MRC-5) cells, unraveling the molecular bases underlying the efficacy and lack of toxicity of this compound.Amaia Marcilla-EtxenikeMaria Laura MartínMaria Antònia Noguera-SalvàJosé Manuel García-VerdugoMario Soriano-NavarroIndranil DeyPablo V EscribáXavier BusquetsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e48235 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Amaia Marcilla-Etxenike Maria Laura Martín Maria Antònia Noguera-Salvà José Manuel García-Verdugo Mario Soriano-Navarro Indranil Dey Pablo V Escribá Xavier Busquets 2-Hydroxyoleic acid induces ER stress and autophagy in various human glioma cell lines.
description	<h4>Background</h4>2-Hydroxyoleic acid is a synthetic fatty acid with potent anti-cancer activity which does not induce undesired side effects. However, the molecular and cellular mechanisms by which this compound selectively kills human glioma cancer cells without killing normal cells is not fully understood. The present study was designed to determine the molecular bases underlying the potency against 1321N1, SF-767 and U118 human glioma cell lines growth without affecting non cancer MRC-5 cells.<h4>Methodology/principal findings</h4>The cellular levels of endoplasmic reticulum (ER) stress, unfolded protein response (UPR) and autophagy markers were determined by quantitative RT-PCR and immunoblotting on 1321N1, SF-767 and U118 human glioma cells and non-tumor MRC-5 cells incubated in the presence or absence of 2OHOA or the ER stress/autophagy inducer, palmitate. The cellular response to these agents was evaluated by fluorescence microscopy, electron microscopy and flow cytometry. We have observed that 2OHOA treatments induced augments in the expression of important ER stress/UPR markers, such as phosphorylated eIF2α, IRE1α, CHOP, ATF4 and the spliced form of XBP1 in human glioma cells. Concomitantly, 2OHOA led to the arrest of 1321N1 cells in the G(2)/M phase of the cell cycle, with down-regulation of cyclin B1 and Cdk1/Cdc2 proteins in the three glioma cell lines studied. Finally, 2OHOA induced autophagy in 1321N1, SF-767 and U118 cells, with the appearance of autophagic vesicles and the up-regulation of LC3BI, LC3BII and ATG7 in 1321N1 cells, increases of LC3BI, LC3BII and ATG5 in SF-767 cells and up-regulation of LC3BI and LC3BII in U118 cells. Importantly, 2OHOA failed to induce such changes in non-tumor MRC-5 cells.<h4>Conclusion/significance</h4>The present results demonstrate that 2OHOA induces ER stress/UPR and autophagy in human glioma (1321N1, SF-767 and U118 cell lines) but not normal (MRC-5) cells, unraveling the molecular bases underlying the efficacy and lack of toxicity of this compound.
format	article
author	Amaia Marcilla-Etxenike Maria Laura Martín Maria Antònia Noguera-Salvà José Manuel García-Verdugo Mario Soriano-Navarro Indranil Dey Pablo V Escribá Xavier Busquets
author_facet	Amaia Marcilla-Etxenike Maria Laura Martín Maria Antònia Noguera-Salvà José Manuel García-Verdugo Mario Soriano-Navarro Indranil Dey Pablo V Escribá Xavier Busquets
author_sort	Amaia Marcilla-Etxenike
title	2-Hydroxyoleic acid induces ER stress and autophagy in various human glioma cell lines.
title_short	2-Hydroxyoleic acid induces ER stress and autophagy in various human glioma cell lines.
title_full	2-Hydroxyoleic acid induces ER stress and autophagy in various human glioma cell lines.
title_fullStr	2-Hydroxyoleic acid induces ER stress and autophagy in various human glioma cell lines.
title_full_unstemmed	2-Hydroxyoleic acid induces ER stress and autophagy in various human glioma cell lines.
title_sort	2-hydroxyoleic acid induces er stress and autophagy in various human glioma cell lines.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/d0a2a546870b47b49d5a2e2429a3d008
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2-Hydroxyoleic acid induces ER stress and autophagy in various human glioma cell lines.

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