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Insights into the mechanims underlyng the antiproliferative potential of a Co(II) coordination compound bearing 1,10-Phenanthroline-5,6-Dione: DNA and protein interaction studies

2014-08Journal article Restricted access
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dc.contributor.authorLuís, Daniela V.
dc.contributor.authorSilva, Joana
dc.contributor.authorTomaz, Ana Isabel
dc.contributor.authorAlmeida, Rodrigo F. M. de
dc.contributor.authorLarguinho, Miguel
dc.contributor.authorBaptista, Pedro V.
dc.contributor.authorMartins, Luisa
dc.contributor.authorSilva, Telma F. S.
dc.contributor.authorBorralho, Pedro M.
dc.contributor.authorRodrigues, Cecília M. P.
dc.contributor.authorRodrigues, António S.
dc.contributor.authorPombeiro, Armando
dc.contributor.authorFernandes, Alexandra R.
dc.date.accessioned2015-08-24T11:38:40Z
dc.date.available2015-08-24T11:38:40Z
dc.date.issued2014-08
dc.description.abstractThe very high antiproliferative activity of [Co(Cl)(H2O)(phendione)(2)][BF4] (phendione is 1,10-phenanthroline-5,6-dione) against three human tumor cell lines (half-maximal inhibitory concentration below 1 mu M) and its slight selectivity for the colorectal tumor cell line compared with healthy human fibroblasts led us to explore the mechanisms of action underlying this promising antitumor potential. As previously shown by our group, this complex induces cell cycle arrest in S phase and subsequent cell death by apoptosis and it also reduces the expression of proteins typically upregulated in tumors. In the present work, we demonstrate that [Co(Cl)(phendione)(2)(H2O)][BF4] (1) does not reduce the viability of nontumorigenic breast epithelial cells by more than 85 % at 1 mu M, (2) promotes the upregulation of proapoptotic Bax and cell-cycle-related p21, and (3) induces release of lactate dehydrogenase, which is partially reversed by ursodeoxycholic acid. DNA interaction studies were performed to uncover the genotoxicity of the complex and demonstrate that even though it displays K (b) (+/- A standard error of the mean) of (3.48 +/- A 0.03) x 10(5) M-1 and is able to produce double-strand breaks in a concentration-dependent manner, it does not exert any clastogenic effect ex vivo, ruling out DNA as a major cellular target for the complex. Steady-state and time-resolved fluorescence spectroscopy studies are indicative of a strong and specific interaction of the complex with human serum albumin, involving one binding site, at a distance of approximately 1.5 nm for the Trp214 indole side chain with log K (b) similar to 4.7, thus suggesting that this complex can be efficiently transported by albumin in the blood plasma.por
dc.identifier.citationLUÍS, Daniel V.; [et al] – Insights into the mechanims underlyng the antiproliferative potential of a Co(II) coordination compound bearing 1,10-Phenanthroline-5,6-Dione: DNA and protein interaction studies. Journal of Biological Inorganic Chemistry. ISSN: 0949-8257. Vol. 19, nr. 6 (2014), pp. 787-803por
dc.identifier.doi10.1007/s00775-014-1110-0
dc.identifier.issn0949-8257
dc.identifier.issn1432-1327
dc.identifier.urihttp://hdl.handle.net/10400.21/4945
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherSpringerpor
dc.subjectCobaltpor
dc.subject1,10-Phenanthroline-5,6-dionepor
dc.subjectApoptosispor
dc.subjectDNA Cleavagepor
dc.subjectHuman Serum Albuminpor
dc.titleInsights into the mechanims underlyng the antiproliferative potential of a Co(II) coordination compound bearing 1,10-Phenanthroline-5,6-Dione: DNA and protein interaction studiespor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage803por
oaire.citation.issue6por
oaire.citation.startPage787por
oaire.citation.titleJournal of Biological Inorganic Chemistrypor
oaire.citation.volume19por
person.familyNameLarguinho
person.familyNameMartins
person.familyNamePombeiro
person.givenNameMiguel
person.givenNameLuisa
person.givenNameArmando
person.identifier637885
person.identifier.ciencia-idE218-E297-A4EA
person.identifier.ciencia-id8311-38FA-CEFB
person.identifier.orcid0000-0001-8492-8786
person.identifier.orcid0000-0002-5403-9352
person.identifier.orcid0000-0001-8323-888X
person.identifier.ridN-4375-2013
person.identifier.ridG-6210-2011
person.identifier.ridI-5945-2012
person.identifier.scopus-author-id8650947800
person.identifier.scopus-author-id7006067269
rcaap.rightsclosedAccesspor
rcaap.typearticlepor
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relation.isAuthorOfPublication8ed70b09-b4d3-4a5d-9f75-12b13a332204
relation.isAuthorOfPublication6d18ff2e-5c33-4010-b1e7-964c72349813
relation.isAuthorOfPublication.latestForDiscovery8ed70b09-b4d3-4a5d-9f75-12b13a332204

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