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Decavanadate and metformin-decavanadate effects in human melanoma cells

dc.contributor.authorde Sousa-Coelho, Ana Luísa
dc.contributor.authorAureliano, Manuel
dc.contributor.authorFraqueza, Gil
dc.contributor.authorSerrão, Gisela
dc.contributor.authorGonçalves, João
dc.contributor.authorSánchez-Lombardo, Irma
dc.contributor.authorLink, Wolfgang
dc.contributor.authorFerreira, Bibiana
dc.date.accessioned2022-12-07T11:24:33Z
dc.date.available2022-12-07T11:24:33Z
dc.date.issued2022
dc.description.abstractDecavanadate is a polyoxometalate (POMs) that has shown extensive biological activities, including antidiabetic and anticancer activity. Importantly, vanadium-based compounds as well as antidiabetic biguanide drugs, such as metformin, have shown to exert therapeutic effects in melanoma. A combination of these agents, the metformin-decavanadate complex, was also recognized for its antidiabetic effects and recently described as a better treatment than the monotherapy with metformin enabling lower dosage in rodent models of diabetes. Herein, we compare the effects of decavanadate and metformin-decavanadate on Ca2+-ATPase activity in sarcoplasmic reticulum vesicles from rabbit skeletal muscles and on cell signaling events and viability in human melanoma cells. We show that unlike the decavanadate-mediated non-competitive mechanism, metformin-decavanadate inhibits Ca2+-ATPase by a mixed-type competitive-non-competitive inhibition with an IC50 value about 6 times higher (87 mu M) than the previously described for decavanadate (15 mu M). We also found that both decavanadate and metformin-decavanadate exert antiproliferative effects on melanoma cells at 10 times lower concentrations than monomeric vanadate. Western blot analysis revealed that both, decavanadate and metformin-decavanadate increased phosphorylation of extracellular signal-regulated kinase (ERK) and serine/ threonine protein kinase AKT signaling proteins upon 24 h drug exposure, suggesting that the anti-proliferative activities of these compounds act independent of growth-factor signaling pathways.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1016/j.jinorgbio.2022.111915pt_PT
dc.identifier.issn0162-0134
dc.identifier.urihttp://hdl.handle.net/10400.1/18596
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectDecavanadatept_PT
dc.subjectMetforminpt_PT
dc.subjectMetformin-decavanadatept_PT
dc.subjectPolyoxometalatespt_PT
dc.subjectPolyoxovanadatespt_PT
dc.subjectSkin cancerMelanomapt_PT
dc.subjectCell signalingpt_PT
dc.titleDecavanadate and metformin-decavanadate effects in human melanoma cellspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FMED-ONC%2F4167%2F2020/PT
oaire.citation.startPage111915pt_PT
oaire.citation.titleJournal of Inorganic Biochemistrypt_PT
oaire.citation.volume235pt_PT
oaire.fundingStream3599-PPCDT
person.familyNameDe Sousa-Coelho
person.familyNameAureliano
person.familyNameFraqueza
person.familyNameSerrão Fernandes
person.familyNameferreira
person.givenNameAna Luísa
person.givenNameManuel
person.givenNameGil
person.givenNameLina Gisela
person.givenNameBibiana
person.identifier584146
person.identifier1179689
person.identifier.ciencia-id691B-A574-28ED
person.identifier.ciencia-idAA14-3490-DC5E
person.identifier.ciencia-id1317-C7C9-5BDA
person.identifier.ciencia-id9517-5590-381E
person.identifier.ciencia-idA311-E925-09C5
person.identifier.orcid0000-0002-8451-4302
person.identifier.orcid0000-0003-4858-3201
person.identifier.orcid0000-0003-2969-9292
person.identifier.orcid0000-0001-9952-2228
person.identifier.orcid0000-0003-4772-9395
person.identifier.ridI-3283-2012
person.identifier.ridA-3552-2013
person.identifier.scopus-author-id6603412860
person.identifier.scopus-author-id54683851800
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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