Author | Silva, Suellen Leila Rocha | |
Author | Baliza, Ingrid Rayssa Souza | |
Author | Dias, Rosane Borges | |
Author | Sales, Caroline Brandi Schlaepfer | |
Author | Rocha, Clarissa Araújo Gurgel | |
Author | Soares, Milena Botelho Pereira | |
Author | Correa, Rodrigo de Souza | |
Author | Batista, Alzir Azevedo | |
Author | Bezerra, Daniel Pereira | |
Access date | 2019-08-13T17:08:42Z | |
Available date | 2019-08-13T17:08:42Z | |
Document date | 2019 | |
Citation | SILVA, Suellen Leila Rocha et al. 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, v. 9, p. 1-11, 2019. | pt_BR |
ISSN | 2045-2322 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/34777 | |
Sponsorship | Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
(CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). R.S. Correa would like to thank the financial support provided by the CNPq (Grant 403588/2016-2 and 308370/2017-1) and FAPEMIG (APQ-01674-18). | pt_BR |
Language | eng | pt_BR |
Publisher | Nature Research | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Carcinoma | pt_BR |
Subject in Portuguese | Câncer Colorretal | pt_BR |
Subject in Portuguese | Apoptose | pt_BR |
Subject in Portuguese | Celulas | pt_BR |
Subject in Portuguese | Morte celular | pt_BR |
Subject in Portuguese | Rutênio | pt_BR |
Title | 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 | pt_BR |
Type | Article | pt_BR |
DOI | 10.1038/s41598-019-47539-0 | |
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 complex induces DNA damage-mediated apoptosis by JNK/p38/ERK1/2 via a p53-independent signaling. The Ru(II)-thymine complex (1 and 2 mg/kg/day) also inhibited HCT116 cell growth in a xenograft model, reducing the tumor mass at 32.6-40.1%. Altogether, indicate that the Ru(II)-thymine complex is a promising anti-colon cancer drug candidate. | 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 | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
Affilliation | Federal University of Bahia. Institute of Health Sciences. Department of Biomorphology. Salvador, BA, Brazil. | 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, Brasil. | pt_BR |
Affilliation | Federal University of São Carlos. Department of Chemistry. São Carlos, SP, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
Subject | Carcinoma | pt_BR |
Subject | Colorectal Neoplasms | pt_BR |
Subject | Apoptosis | pt_BR |
Subject | Cells | pt_BR |
Subject | Cell Death | pt_BR |
Subject | Ruthenium | pt_BR |