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New water-soluble Ruthenium(II) cytotoxic complex: biological activity and celular distribution

2014-01Journal article Restricted access
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dc.contributor.authorMorais, Tânia S.
dc.contributor.authorSantos, Filipa C.
dc.contributor.authorJorge, Tiago F.
dc.contributor.authorCôrte-Real, Leonor
dc.contributor.authorMadeira, Paulo J. Amorim
dc.contributor.authorMarques, Fernanda
dc.contributor.authorRobalo, Maria Paula
dc.contributor.authorMatos, António
dc.contributor.authorSantos, Isabel
dc.contributor.authorGarcia, M. Helena
dc.date.accessioned2015-08-24T13:34:46Z
dc.date.available2015-08-24T13:34:46Z
dc.date.issued2014-01
dc.description.abstractA novel water soluble organometallic compound, [RuCp(mTPPMSNa)(2,2'-bipy)][CF3SO3] (TM85, where Cp=eta(5)-cyclopentadienyl, mTPPMS = diphenylphosphane-benzene-3-sulfonate and 2,2'-bipy = 2,2'-bipyridine) is presented herein. Studies of interactions with relevant proteins were performed to understand the behavior and mode of action of this complex in the biological environment. Electrochemical and fluorescence studies showed that TM85 strongly binds to albumin. Studies carried out to study the formation of TM85 which adducts with ubiquitin and cytochrome c were performed by electrospray ionization mass spectrometry (ESI-MS). Antitumor activity was evaluated against a variety of human cancer cell lines, namely A2780, A2780cisR, MCF7, MDAMB231, HT29, PC3 and V79 non-tumorigenic cells and compared with the reference drug cisplatin. TM85 cytotoxic effect was reduced in the presence of endocytosis modulators at low temperatures, suggesting an energy-dependent mechanism consistent with endocytosis. Ultrastructural analysis by transmission electron microscopy (TEM) revealed that TM85 targets the endomembranar system disrupting the Golgi and also affects the mitochondria. Disruption of plasma membrane observed by flow cytometry could lead to cellular damage and cell death. On the whole, the biological activity evaluated herein combined with the water solubility property suggests that complex TM85 could be a promising anticancer agent. (C) 2013 Elsevier Inc. All rights reserved.por
dc.identifier.citationMORAIS, Tânia S.; [et al] – New water-soluble Ruthenium(II) Cytotoxic Complex: biological activity and celular distribution. Journal of Inorganic Biochemistry. ISSN: 0162-0134. Vol. 130 (2014), pp. 1-14por
dc.identifier.doi10.1016/j.jinorgbio.2013.09.013
dc.identifier.issn0162-0134
dc.identifier.issn1873-3344
dc.identifier.urihttp://hdl.handle.net/10400.21/4953
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherElsevier Science Incpor
dc.subjectRutheniumpor
dc.subjectCyclopentadienylpor
dc.subjectCytotoxicitypor
dc.subjectCellular Uptakepor
dc.subjectAlbuminpor
dc.subjectUbiquitinpor
dc.titleNew water-soluble Ruthenium(II) cytotoxic complex: biological activity and celular distributionpor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage14por
oaire.citation.startPage1por
oaire.citation.titleJournal of Inorganic Biochemistrypor
oaire.citation.volume130por
person.familyNameCôrte-Real
person.familyNameRobalo
person.familyNameAnselmo Viegas Garcia
person.givenNameLeonor
person.givenNameMaria Paula
person.givenNameMaria Helena
person.identifierH-2175-­2013
person.identifier.ciencia-idF112-59D7-0984
person.identifier.ciencia-idE11C-A704-9C18
person.identifier.ciencia-id5414-9AEF-4194
person.identifier.orcid0000-0002-4974-1075
person.identifier.orcid0000-0002-8200-6910
person.identifier.orcid0000-0002-4344-2218
person.identifier.ridH-5636-2013
person.identifier.ridB-2002-2012
person.identifier.scopus-author-id55627880500
person.identifier.scopus-author-id9269662100
person.identifier.scopus-author-id6507884466
rcaap.rightsclosedAccesspor
rcaap.typearticlepor
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relation.isAuthorOfPublication823a9498-17ab-451f-bb8f-56338643ac0c
relation.isAuthorOfPublicationddef2398-fb7d-4551-a9fe-71c411d1d706
relation.isAuthorOfPublication.latestForDiscoveryddef2398-fb7d-4551-a9fe-71c411d1d706

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