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dc.contributor.authorFernández Gil, Beatriz Irene
dc.contributor.authorEscames Rosa, Germaine 
dc.date.accessioned2022-12-02T09:40:29Z
dc.date.available2022-12-02T09:40:29Z
dc.date.issued2022-11-02
dc.identifier.citationFernandez-Gil, B.I.; Otamendi-Lopez, A.; Bechtle, A.; Vazquez-Ramos, C.A.; Qosja, N.; Suarez-Meade, P.; Sarabia-Estrada, R.; Jentoft, M.E.; Guerrero-Cázares, H.; Escames, G.; et al. Melatonin Treatment Triggers Metabolic and Intracellular pH Imbalance in Glioblastoma. Cells 2022, 11, 3467. [https://doi.org/10.3390/cells11213467]es_ES
dc.identifier.urihttps://hdl.handle.net/10481/78242
dc.descriptionSupplementary Materials The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/cells11213467/s1, Figure S1: Metabolic baseline characterization, treatments with melatonin agonists, and combina-tion treatments of melatonin (aMT) and the standard of care for GBM; Figure S2: Seahorse com-plementary analyses; Figure S3: pH fluctuations; Figure S4: In vivo results after melatonin intra-tumoral treatment.es_ES
dc.descriptionFunding This research was funded by the Distinguished Mayo Clinic Investigator Award (A.Q.-H.) and the William J. and Charles H. Mayo Professor (A.Q.-H.); the Uihlein Neuro-oncology Research Fund (A.Q.-H.) and R01CA200399 (A.Q.-H.).es_ES
dc.description.abstractMetabolic rewiring in glioblastoma (GBM) is linked to intra- and extracellular pH regulation. In this study, we sought to characterize the role of melatonin on intracellular pH modulation and metabolic consequences to identify the mechanisms of action underlying melatonin oncostatic effects on GBM tumor initiating cells. GBM tumor initiating cells were treated at different times with melatonin (1.5 and 3.0 mM).We analyzed melatonin’s functional effects on GBM proliferation, cell cycle, viability, stemness, and chemo-radiosensitivity. We then assessed the effects of melatonin on GBM metabolism by analyzing the mitochondrial and glycolytic parameters. We also measured the intracellular and extracellular pH. Finally, we tested the effects of melatonin on a mouse subcutaneous xenograft model. We found that melatonin downregulated LDHA and MCT4, decreasing lactate production and inducing a decrease in intracellular pH that was associated with an increase in ROS and ATP depletion. These changes blocked cell cycle progression and induced cellular death and we observed similar results in vivo. Melatonin’s cytotoxic effects on GBM were due, at least in part, to intracellular pH modulation, which has emerged as a newly identified mechanism, providing new insights into the oncostatic effect of melatonin on GBM.es_ES
dc.description.sponsorshipDistinguished Mayo Clinic Investigator Award (A.Q.-H.)es_ES
dc.description.sponsorshipWilliam J. and Charles H. Mayo Professor (A.Q.-H.)es_ES
dc.description.sponsorshipUihlein Neuro-oncology Research Fund (A.Q.-H.)es_ES
dc.description.sponsorshipR01CA200399 (A.Q.-H.)es_ES
dc.language.isoenges_ES
dc.publisherMDPIes_ES
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectIntracellular acidityes_ES
dc.subjectCancer metabolismes_ES
dc.subjectLactatees_ES
dc.subjectMCT4es_ES
dc.subjectROSes_ES
dc.subjectLDHAes_ES
dc.subjectGBMes_ES
dc.subjectOXPHOSes_ES
dc.subjectGlycolysises_ES
dc.titleMelatonin Treatment Triggers Metabolic and Intracellular pH Imbalance in Glioblastomaes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES
dc.identifier.doi10.3390/cells11213467
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersiones_ES


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Atribución 4.0 Internacional
Except where otherwise noted, this item's license is described as Atribución 4.0 Internacional