Ru(II)-thymine complex causes DNA damage and apoptotic cell death in human colon carcinoma HCT116 cells mediated by JNK/p38/ERK1/2 via a p53-independent signaling

Scientific Reports
Suellen L R SilvaDaniel P Bezerra

Abstract

Ru(II)-thymine complex [Ru(PPh3)2(Thy)(bipy)]PF6 (where PPh3 = triphenylphosphine, Thy = thyminate and bipy = 2,2'-bipyridine) is a potent cytotoxic agent with ability to bind to DNA, inducing caspase-mediated apoptosis in leukemia cells. In this study, we investigated the mechanism underlying the cell death induction by Ru(II)-thymine complex in human colon carcinoma HCT116 cells, as well as its effect in xenograft tumor model. The Ru(II)-thymine complex increased significantly the percentage of apoptotic HCT116 cells. Co-treatment with a JNK/SAPK inhibitor, p38 MAPK inhibitor and MEK inhibitor, which inhibit the activation of ERK1/2, caused a marked reduction of the percentage of complex-induced apoptotic cells. Moreover, the Ru(II)-thymine complex induced an increase in phospho-JNK2 (T183/Y185), phospho-p38α (T180/Y182) and phospho-ERK1 (T202/Y204) levels in HCT116 cells. Treatment with the Ru(II)-thymine complex increased significantly the phospho-histone H2AX (S139) expression, a DNA damage marker. The expression of phospho-p53 (S15) and MDM2 were not changed, and the co-treatment with a p53 inhibitor (cyclic pifithrin-α) did not reduce the complex-induced apoptosis in HCT116 cells, indicating that the Ru(II)-thymine compl...Continue Reading

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Citations

Apr 4, 2020·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Felipe Pantoja MesquitaRaquel Carvalho Montenegro
May 1, 2021·International Journal of Molecular Sciences·Marta Orts-ArroyoJosé Martínez-Lillo
Feb 26, 2020·Inorganic Chemistry·Nicholas P ToupinJeremy J Kodanko
Aug 29, 2021·Pharmaceutics·Kazi Mustafa MahmudMd Asiful Islam

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Methods Mentioned

BETA
xenograft
flow cytometry
ELISA
xenografts
Protein Assay

Software Mentioned

GraphPad Prism
BD FACSDiva
FlowJo

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Apoptosis

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