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Therapeutic potential of vanadium complexes with 1,10-phenanthroline ligands, quo vadis? Fate of complexes in cell media and cancer cells

2021-04Journal article Restricted access
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dc.contributor.authorNunes, Patrique
dc.contributor.authorCorreia, Isabel
dc.contributor.authorCavaco, Isabel
dc.contributor.authorMarques, Fernanda
dc.contributor.authorPinheiro, Teresa
dc.contributor.authorAvecilla, Fernando
dc.contributor.authorPessoa, Joao Costa
dc.date.accessioned2021-09-08T10:58:00Z
dc.date.available2021-09-08T10:58:00Z
dc.date.issued2021-04
dc.description.abstract(VO)-O-IV-complexes formulated as [(VO)-O-IV(OSO3)(phen)(2)] (1) (phen = 1,10-phenanthroline), [(VO)-O-IV(OSO3) (Me(2)phen)(2)] (2) (Me(2)phen = 4,7-dimethyl-1,10-phenanthroline) and [(VO)-O-IV(OSO3)(amphen)(2)] (3) (amphen = 5-amino-1,10-phenanthroline) were prepared and stability in cell incubation media evaluated. Their cytotoxicity was determined against the A2780 (ovarian), MCF7 (breast) and PC3 (prostate) human cancer cells at different incubation times. While at 3 and 24 h the cytotoxicity differs for complexes and corresponding free ligands, at 72 h incubation all compounds are equally active presenting low IC50 values. Upon incubation of A2780 cells with 1-3, cellular distribution of vanadium in cytosol, membranes, nucleus and cytoskeleton, indicate that the uptake of V is low, particularly for 1, and that the uptake pattern depends on the ligand. Nuclear microscopic techniques are used for imaging and elemental quantification in whole PC3 cells incubated with 1. Once complexes are added to cell culture media, they decompose, and with time most V-IV oxidizes to V-V-species. Modeling of speciation when [(VO)-O-IV(OSO3)(phen)(2)] (1) is added to cell media is presented. At lower concentrations of 1, (VO)-O-IV- and phen-containing species are mainly bound to bovine serum albumin, while at higher concentrations [(VO)-O-IV (phen)n](2+)-complexes become relevant, being predicted that the species taken up and mechanisms of action operating depend on the total concentration of complex. This study emphasizes that for these (VO)-O-IV-systems, and probably for many others involving oxidovanadium or other labile metal complexes, it is not possible to identify active species or propose mechanisms of cytotoxic action without evaluating speciation occurring in cell media.
dc.description.sponsorshipCentro de Quimica Estrutural; Centro de Quimica Estrutural - Fundacao para a Ciencia e Tecnologia (FCT) [UID/BIO/04565/2020, UIDB/00100/2020, UID/Multi/04349/2019]; Centro de Ciencias e Tecnologias Nucleares - Fundacao para a Ciencia e Tecnologia (FCT) [UID/BIO/04565/2020, UIDB/00100/2020, UID/Multi/04349/2019]; Programa Operacional Regional de Lisboa 2020 [007317]; FCTPortuguese Foundation for Science and TechnologyEuropean Commission [IF/00841/2012]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1016/j.jinorgbio.2020.111350
dc.identifier.issn0162-0134
dc.identifier.urihttp://hdl.handle.net/10400.1/17001
dc.language.isoeng
dc.peerreviewedyes
dc.publisherElsevier
dc.relationCentro de Química Estrutural
dc.relationCentre for Nuclear Sciences and Technologies
dc.relationInteraction of biomacromolecules with ionic liquids
dc.relationInstitute for Bioengineering and Biosciences
dc.subjectVanadium complexes
dc.subject1,10-phenanthroline
dc.subjectCytotoxicity
dc.subjectSpeciation
dc.subjectCell incubation media
dc.subjectCell uptake
dc.subject.otherBiochemistry & Molecular Biology; Chemistry
dc.titleTherapeutic potential of vanadium complexes with 1,10-phenanthroline ligands, quo vadis? Fate of complexes in cell media and cancer cells
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCentro de Química Estrutural
oaire.awardTitleCentre for Nuclear Sciences and Technologies
oaire.awardTitleInteraction of biomacromolecules with ionic liquids
oaire.awardTitleInstitute for Bioengineering and Biosciences
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00100%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMulti%2F04349%2F2019/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Investigador FCT/IF%2F00841%2F2012%2FCP0171%2FCT0009/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04565%2F2020/PT
oaire.citation.startPage111350
oaire.citation.titleJournal of Inorganic Biochemistry
oaire.citation.volume217
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamInvestigador FCT
oaire.fundingStream6817 - DCRRNI ID
person.familyNamePALMA ANTUNES CAVACO
person.givenNameISABEL MARIA
person.identifierH-9087-2012
person.identifier.ciencia-idD515-FB5E-1205
person.identifier.orcid0000-0001-8651-9054
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccess
rcaap.typearticle
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