Author | Oliveira, Maiara de Souza | |
Author | Santana, Ádila Angélica Dantas de | |
Author | Correa, Rodrigo S | |
Author | Soares, Milena Botelho Pereira | |
Author | Batista, Alzir Azevedo | |
Author | Bezerra, Daniel Pereira | |
Access date | 2018-06-29T16:37:13Z | |
Available date | 2018-06-29T16:37:13Z | |
Document date | 2018 | |
Citation | OLIVEIRA, M. S. et al. Ru(II)-Thymine Complex Causes Cell Growth Inhibition and Induction of Caspase-Mediated Apoptosis in Human Promyelocytic Leukemia HL-60 Cells. International Journal of Molecular Sciences, v. 19, p. 1609, 2018. | pt_BR |
ISSN | 1661-6596 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/27202 | |
Sponsorship | Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). In particular, R.S.C. would like to thank CNPq for the grants #403588/2016-2 and #308370/2017-1. | pt_BR |
Language | eng | pt_BR |
Publisher | MDPI | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Rutênio | pt_BR |
Subject in Portuguese | Timina | pt_BR |
Subject in Portuguese | Citotoxicidade | pt_BR |
Subject in Portuguese | Apoptose | pt_BR |
Subject in Portuguese | HL-60 | pt_BR |
Title | Ru(II)-Thymine Complex Causes Cell Growth Inhibition and Induction of Caspase-Mediated Apoptosis in Human Promyelocytic Leukemia HL-60 Cells | pt_BR |
Type | Article | pt_BR |
DOI | 10.3390/ijms19061609 | |
Abstract | 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. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Federal University of Ouro Preto. Department of Chemistry. Ouro Preto, MG, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Center of Biotechnology and Cell Therapy. Salvador, BA, Brazil | pt_BR |
Affilliation | Federal University of São Carlos. Department of Chemistry. São Carlos, SP, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Subject | Ruthenium | pt_BR |
Subject | Thymine | pt_BR |
Subject | Cytotoxicity | pt_BR |
Subject | Apoptosis | pt_BR |
Subject | HL-60 | pt_BR |