Cytoxicity and Apoptotic Mechanism of Ruthenium(II) Amino Acid Complexes in Sarcoma-180 Tumor Cells

dc.contributor.authorLima, Aliny Pereira
dc.contributor.authorPereira, Flavia Castro
dc.contributor.authorPinheiro Almeida, Marcio Aurelio
dc.contributor.authorSantos Mello, Francyelli Mariana
dc.contributor.authorPires, Wanessa Carvalho
dc.contributor.authorPinto, Thallita Monteiro
dc.contributor.authorDelella, Flavia Karina [UNESP]
dc.contributor.authorFelisbino, Sergio Luis [UNESP]
dc.contributor.authorMoreno, Virtudes
dc.contributor.authorBatista, Alzir Azevedo
dc.contributor.authorSilveira-Lacerda, Elisangela de Paula
dc.contributor.institutionUniversidade Federal de Goiás (UFG)
dc.contributor.institutionUniv Fed Maranhao
dc.contributor.institutionUniversidade Federal de São Carlos (UFSCar)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniv Barcelona
dc.description.abstractOver the past several decades, much attention has been focused on ruthenium complexes in antitumor therapy. Ruthenium is a transition metal that possesses several advantages for rational antitumor drug design and biological applications. In the present study, five ruthenium complexes containing amino acids were studied in vitro to determine their biological activity against sarcoma-180 tumor cells. The cytotoxicity of the complexes was evaluated by an MTT assay, and their mechanism of action was investigated. The results demonstrated that the five complexes inhibited the growth of the S180 tumor cell line, with IC50 values ranging from 22.53 mu M to 50.18 mu M, and showed low cytotoxicity against normal L929 fibroblast cells. Flow cytometric analysis revealed that the [Ru(gly)(bipy)(dppb)] PF6 complex (2) inhibited the growth of the tumor cells by inducing apoptosis, as evidenced by an increased number of Annexin V-positive cells and G0/G1 phase cell cycle arrest. Further investigation showed that complex 2 caused a loss of mitochondrial membrane potential; activated caspases 3, caspase-8, and caspase-9 and caused a change in the mRNA expression levels of caspase 3, caspase-9 as well as the bax genes. The levels of the pro-apoptotic Bcl-2 family protein Bak were increased. Thus, we demonstrated that ruthenium amino acid complexes are promising drugs against S180 tumor cells, and we recommend further investigations of their role as chemotherapeutic agents for sarcomas.en
dc.description.affiliationUniv Fed Goias, Inst Biol Sci, Lab Mol Genet & Cytogen, Goiania, Go, Brazil
dc.description.affiliationUniv Fed Maranhao, Sao Luis, Maranhao, Brazil
dc.description.affiliationUniv Fed Sao Carlos, Dept Chem, BR-13560 Sao Carlos, SP, Brazil
dc.description.affiliationUNESP, Inst Biosci, Dept Morphol, Botucatu, SP, Brazil
dc.description.affiliationUniv Barcelona, Dept Inorgan Chem, Barcelona, Spain
dc.description.affiliationUnespUNESP, Inst Biosci, Dept Morphol, Botucatu, SP, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipFoundation for Research and Scientific and Technological Development of Maranhao-FAPEMA
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIdFAPESP: 12/06013-4
dc.description.sponsorshipIdFAPEMA: 00629/2008
dc.description.sponsorshipIdCNPq: 141648/2010-4
dc.identifier.citationPlos One. San Francisco: Public Library Science, v. 9, n. 10, 11 p., 2014.
dc.publisherPublic Library Science
dc.relation.ispartofPlos One
dc.rights.accessRightsAcesso aberto
dc.sourceWeb of Science
dc.titleCytoxicity and Apoptotic Mechanism of Ruthenium(II) Amino Acid Complexes in Sarcoma-180 Tumor Cellsen
dcterms.rightsHolderPublic Library Science
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências, Botucatupt


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