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Ru(II)-Thymine Complex Causes Cell Growth Inhibition and Induction of Caspase-Mediated Apoptosis in Human Promyelocytic Leukemia HL-60 Cells.
de Souza Oliveira, Maiara; de Santana, Ádila Angélica Dantas; Correa, Rodrigo S; Soares, Milena Botelho Pereira; Batista, Alzir Azevedo; Bezerra, Daniel Pereira.
Afiliação
  • de Souza Oliveira M; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Rua Waldemar Falcão, 121, Candeal, Salvador 40296-710, Bahia, Brazil. msoliveira87@hotmail.com.
  • de Santana ÁAD; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Rua Waldemar Falcão, 121, Candeal, Salvador 40296-710, Bahia, Brazil. dantas.adila@gmail.com.
  • Correa RS; Department of Chemistry, Federal University of Ouro Preto, Ouro Preto 35400-000, Minas Gerais, Brazil. rodrigoquimic@gmail.com.
  • Soares MBP; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Rua Waldemar Falcão, 121, Candeal, Salvador 40296-710, Bahia, Brazil. milenabpsoares@gmail.com.
  • Batista AA; Center of Biotechnology and Cell Therapy, Hospital São Rafael, Salvador 41253-190, Bahia, Brazil. milenabpsoares@gmail.com.
  • Bezerra DP; Department of Chemistry, Federal University of São Carlos, São Carlos 13561-901, São Paulo, Brazil. daab@ufscar.br.
Int J Mol Sci ; 19(6)2018 May 30.
Article em En | MEDLINE | ID: mdl-29848969
Ruthenium-based compounds represent a class of potential antineoplastic drugs. Recently, we designed, synthesized, and identified the Ru(II)-thymine complex [Ru(PPh3)2(Thy)(bipy)]PF6 (where PPh = triphenylphosphine, Thy = thymine and bipy = 2,2'-bipyridine) as a potent cytotoxic agent with the ability to bind to DNA and human and bovine serum albumins. In this study, the underlying cytotoxic mechanism of the [Ru(PPh3)2(Thy)(bipy)]PF6 complex was assessed. This complex displayed potent cytotoxicity in different cancer cell lines; the morphology that is associated with apoptotic cell death, increased internucleosomal DNA fragmentation without cell membrane permeability, loss of the mitochondrial transmembrane potential, increased phosphatidylserine externalization, and caspase-3 activation were observed in human promyelocytic leukemia HL-60 cells that were treated with the complex. Moreover, pretreatment of HL-60 cells with Z-VAD(OMe)-FMK, a pan-caspase inhibitor, partially reduced the apoptosis that was induced by the complex, indicating that the apoptotic cell death occurred through a caspase-mediated pathway. In conclusion, the [Ru(PPh3)2(Thy)(bipy)]PF6 complex displays potent cytotoxicity to different cancer cells and induces caspase-mediated apoptosis in HL-60 cells.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Timina / Compostos de Rutênio / Caspases Tipo de estudo: Etiology_studies Limite: Animals / Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Timina / Compostos de Rutênio / Caspases Tipo de estudo: Etiology_studies Limite: Animals / Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça