Ru(II)-thymine complex causes cell growth inhibition and induction of caspase-mediated apoptosis in human promyelocytic leukemia HL-60 cells.
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Date
2018
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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.
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Keywords
Ruthenium, Cytotoxicity
Citation
OLIVEIRA, M. de 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, n. 6, p. 1-13, maio 2018. Disponível em: <https://www.mdpi.com/1422-0067/19/6/1609>. Acesso em: 7 mar. 2019.