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Cis-[RuCl(BzCN)(N-N)(P-P)]PF6 complexes: Synthesis and in vitro antitumor activity: (BzCN=benzonitrile; N-N=2,2'-bipyridine; 1,10-phenanthroline; P-P=1,4-bis(diphenylphosphino) butane, 1,2-bis(diphenylphosphino)ethane, or 1,1'-(diphenylphosphino)ferrocene).
Pereira, Flávia de C; Lima, Benedicto A V; de Lima, Aliny P; Pires, Wanessa C; Monteiro, Thallita; Magalhães, Lorena F; Costa, Wanderson; Graminha, Angélica E; Batista, Alzir A; Ellena, Javier; Siveira-Lacerda, Elisângela de P.
Afiliação
  • Pereira Fde C; Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás - UFG, Goiânia, GO CEP 74001-970, Brazil.
  • Lima BA; Department of Chemistry, Federal University of São Carlos, São Carlos, SP CEP 13.565-905, Brazil.
  • de Lima AP; Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás - UFG, Goiânia, GO CEP 74001-970, Brazil.
  • Pires WC; Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás - UFG, Goiânia, GO CEP 74001-970, Brazil.
  • Monteiro T; Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás - UFG, Goiânia, GO CEP 74001-970, Brazil.
  • Magalhães LF; Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás - UFG, Goiânia, GO CEP 74001-970, Brazil.
  • Costa W; Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás - UFG, Goiânia, GO CEP 74001-970, Brazil.
  • Graminha AE; Department of Chemistry, Federal University of São Carlos, São Carlos, SP CEP 13.565-905, Brazil.
  • Batista AA; Department of Chemistry, Federal University of São Carlos, São Carlos, SP CEP 13.565-905, Brazil. Electronic address: daab@ufscar.br.
  • Ellena J; São Carlos Institute of Physics, University of São Paulo, São Carlos, SP CEP 13560-970, Brazil.
  • Siveira-Lacerda Ede P; Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás - UFG, Goiânia, GO CEP 74001-970, Brazil. Electronic address: silveiralacerda@gmail.com.
J Inorg Biochem ; 149: 91-101, 2015 Aug.
Article em En | MEDLINE | ID: mdl-25873134
The motivation to use ruthenium complexes in cancer treatment has led our research group to synthesize complexes with this metal and test them against several types of tumor cells, yielding promising results. In this paper the results of biological tests, assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, were carried out on the complexes cis-[RuCl(BzCN)(bipy)(dppe)]PF6 (1), cis-[RuCl(BzCN)(bipy)(dppb)]PF6 (2), cis-[RuCl(BzCN)(bipy)(dppf)]PF6 (3) and cis-[RuCl(BzCN)(phen)(dppb)]PF6 (4) which are described [BzCN = b enzonitrile; bipy = 2,2'-bipyridine; phen = 1,10-phenanthroline; dppe = 1,2-bis(diphenylphosphino) ethane; dppb = 1,4-bis-(diphenylphosphino)butane; dppf = 1,1'-bis(diphenylphosphino)ferrocene]. The present study is focused on the cytotoxic activity of complexes (1)-(4) against four tumor cell lines and on the apoptosis and changes in the cell cycle and gene expression observed in the sarcoma 180 (S180) tumor cell line treated with complex (1). The results demonstrated that this complex inhibits S180 cell growth, with an IC50 of 17.02 ± 8.21 µM, while exhibiting lower cytotoxicity (IC50 = 53.73 ± 5.71 µM) towards lymphocytes (normal cells). Flow cytometry revealed that the complex inhibits the growth of tumor cells by inducing apoptosis as evidenced by an increase in the proportion of cells positive for annexin V staining and G0/G1 phase cell-cycle arrest. Further investigation showed that complex (1) induces a drop in the mitochondrial membrane potential and provokes a decrease in Bcl-2 protein expression and increase in caspase 3 activation, while the increased activation of caspase 8 caused a decrease in the gene expression in caspases 3 and 9. Increases in Tp53 and Bax expressions were also observed.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Rutênio / Complexos de Coordenação / Antineoplásicos Limite: Animals / Humans Idioma: En Revista: J Inorg Biochem Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Rutênio / Complexos de Coordenação / Antineoplásicos Limite: Animals / Humans Idioma: En Revista: J Inorg Biochem Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos