Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/45043
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dc.contributor.authorLamego, Inês-
dc.contributor.authorDuarte, Iola F.-
dc.contributor.authorMarques, M. Paula M.-
dc.contributor.authorGil, Ana M.-
dc.date.accessioned2017-12-15T16:15:17Z-
dc.date.available2017-12-15T16:15:17Z-
dc.date.issued2014-01-01-
dc.identifier10.1021/pr500907d-
dc.identifier.urihttp://hdl.handle.net/10316/45043-
dc.description.abstractA high resolution magic angle spinning NMR metabolomics study of the effects of doxorubicin (DOX), methotrexate (MTX) and cisplatin (cDDP) on MG-63 cells is presented and unveils the cellular metabolic adaptations to these drugs, often used together in clinical protocols. Although cDDP-treated cells were confirmed to undergo extensive membrane degradation accompanied by increased neutral lipids, DOX- and MTX-treated cells showed no lipids increase and different phospholipid signatures, which suggests that (i) DOX induces significant membrane degradation, decreased membrane synthesis, and apparent inhibition of de novo lipid synthesis, and (ii) MTX induces decreased membrane synthesis, while no membrane disruption or de novo lipid synthesis seem to occur. Nucleotide signatures were in apparent agreement with the different drug action mechanisms, a link having been found between UDP-GlcNAc and the active pathways of membrane degradation and energy metabolism, for cDDP and DOX, with a relation to oxidative state and DNA degradation, for cDDP. Correlation studies unveiled drug-specific antioxidative signatures, which pinpointed m- and s-inositols, taurine, glutamate/glutamine, and possibly creatine as important in glutathione metabolism. These results illustrate the ability of NMR metabolomics to measure cellular responses to different drugs, a first step toward understanding drug synergism and the definition of new biomarkers of drug efficacy.por
dc.language.isoengpor
dc.rightsopenAccesspor
dc.subjectAmino Acidspor
dc.subjectAntineoplastic Agentspor
dc.subjectBiomarkers, Tumorpor
dc.subjectCell Line, Tumorpor
dc.subjectCell Membranepor
dc.subjectCholinepor
dc.subjectCisplatinpor
dc.subjectDoxorubicinpor
dc.subjectEnergy Metabolismpor
dc.subjectHumanspor
dc.subjectLipid Metabolismpor
dc.subjectMagnetic Resonance Spectroscopypor
dc.subjectMetabolic Networks and Pathwayspor
dc.subjectMetabolomepor
dc.subjectMetabolomicspor
dc.subjectMethotrexatepor
dc.subjectMolecular Structurepor
dc.subjectMultivariate Analysispor
dc.subjectNucleotidespor
dc.subjectOsteosarcomapor
dc.titleMetabolic Markers of MG-63 Osteosarcoma Cell Line Response to Doxorubicin and Methotrexate Treatment: Comparison to Cisplatinpor
dc.typearticle-
degois.publication.firstPage6033por
degois.publication.lastPage6045por
degois.publication.issue12por
degois.publication.titleJournal of Proteome Researchpor
dc.peerreviewedyespor
dc.identifier.doi10.1021/pr500907dpor
degois.publication.volume13por
item.fulltextCom Texto completo-
item.languageiso639-1en-
item.grantfulltextopen-
Appears in Collections:FCTUC Ciências da Vida - Artigos em Revistas Internacionais
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