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dc.contributor.authorDuraj, Tomás
dc.contributor.authorGarcía Romero, Noemí 
dc.contributor.authorCarrión Navarro, Josefa
dc.contributor.authorMadurga Lacalle, Rodrigo 
dc.contributor.authorOrtiz de Mendivil, Ana
dc.contributor.authorPrat Acin, Ricardo
dc.contributor.authorGarcia Cañamaque, Lina
dc.contributor.authorAyuso Sacido, Ángel 
dc.date.accessioned2021-02-11T09:57:03Z
dc.date.available2021-02-11T09:57:03Z
dc.date.issued2021
dc.identifier.issn2073-4409spa
dc.identifier.urihttp://hdl.handle.net/10641/2215
dc.description.abstractGlioblastoma (GBM) is the most aggressive primary brain tumor, with a median survival at diagnosis of 16–20 months. Metabolism represents a new attractive therapeutic target; however, due to high intratumoral heterogeneity, the application of metabolic drugs in GBM is challenging. We characterized the basal bioenergetic metabolism and antiproliferative potential of metformin (MF), dichloroacetate (DCA), sodium oxamate (SOD) and diazo-5-oxo-L-norleucine (DON) in three distinct glioma stem cells (GSCs) (GBM18, GBM27, GBM38), as well as U87MG. GBM27, a highly oxidative cell line, was the most resistant to all treatments, except DON. GBM18 and GBM38, Warburg-like GSCs, were sensitive to MF and DCA, respectively. Resistance to DON was not correlated with basal metabolic phenotypes. In combinatory experiments, radiomimetic bleomycin exhibited therapeutically relevant synergistic effects with MF, DCA and DON in GBM27 and DON in all other cell lines. MF and DCA shifted the metabolism of treated cells towards glycolysis or oxidation, respectively. DON consistently decreased total ATP production. Our study highlights the need for a better characterization of GBM from a metabolic perspective. Metabolic therapy should focus on both glycolytic and oxidative subpopulations of GSCs.spa
dc.language.isoengspa
dc.publisherCellsspa
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 España*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/*
dc.subjectGlioblastomaspa
dc.subjectEnergy metabolismspa
dc.subjectGlycolysisspa
dc.subjectOxidative phosphorylationspa
dc.titleBeyond the Warburg Effect: Oxidative and Glycolytic Phenotypes Coexist within the Metabolic Heterogeneity of Glioblastoma.spa
dc.typejournal articlespa
dc.type.hasVersionAMspa
dc.rights.accessRightsopen accessspa
dc.description.extent3439 KBspa
dc.identifier.doi10.3390/cells10020202spa
dc.relation.publisherversionhttps://www.mdpi.com/2073-4409/10/2/202spa


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