| Author | Bomfim, Larissa Mendes | |
| Author | Araujo, Fênix A. de | |
| Author | Dias, Rosane Borges | |
| Author | Sales, Caroline Brandi Schlaepfer | |
| Author | Rocha, Clarissa Araújo Gurgel | |
| Author | Correa, Rodrigo de Sousa | |
| Author | Soares, Milena Botelho Pereira | |
| Author | Batista, Alzir Azevedo | |
| Author | Bezerra, Daniel Pereira | |
| Access date | 2019-10-08T14:32:30Z | |
| Available date | 2019-10-08T14:32:30Z | |
| Document date | 2019 | |
| Citation | BOMFIM, Larissa Mendes et al. Ruthenium(II) complexes with 6-methyl-2-thiouracil selectively reduce cell proliferation, cause DNA double-strand break and trigger caspase-mediated apoptosis through JNK/p38 pathways in human acute promyelocytic leukemia cells. Scientific Reports, v. 9, p. 1-17, 2019. | pt_BR |
| ISSN | 2045-2322 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/36263 | |
| Language | eng | pt_BR |
| Publisher | Nature Research | pt_BR |
| Rights | open access | pt_BR |
| Subject in Portuguese | Compostos de Rutênio | pt_BR |
| Subject in Portuguese | Leucemia de Células | pt_BR |
| Subject in Portuguese | Proliferação Celular | pt_BR |
| Subject in Portuguese | Humanos | pt_BR |
| Title | Ruthenium(II) complexes with 6-methyl-2-thiouracil selectively reduce cell proliferation, cause DNA double-strand break and trigger caspase-mediated apoptosis through JNK/p38 pathways in human acute promyelocytic leukemia cells | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.1038/s41598-019-47914-x | |
| Abstract | Ruthenium(II) complexes with 6-methyl-2-thiouracil cis-[Ru(6m2tu)2(PPh3)2] (1) and [Ru(6m2tu)2(dppb)] (2) (where PPh3 = triphenylphosphine; dppb = 1,4-bis(diphenylphosphino)butane; and 6m2tu = 6-methyl-2-thiouracil) are potent cytotoxic agents and able to bind DNA. The aim of this study was to evaluate in vitro cellular underlying mechanism and in vivo effectiveness of these ruthenium(II) complexes in human acute promyelocytic leukemia HL-60 cells. Both complexes displayed potent and selective cytotoxicity in myeloid leukemia cell lines, and were detected into HL-60 cells. Reduction of the cell proliferation and augmented phosphatidylserine externalization, caspase-3, -8 and -9 activation and loss of mitochondrial transmembrane potential were observed in HL-60 cells treated with both complexes. Cotreatment with Z-VAD(OMe)-FMK, a pan-caspase inhibitor, reduced Ru(II) complexes-induced apoptosis. In addition, both metal complexes induced phosphorylation of histone H2AX (S139), JNK2 (T183/Y185) and p38α (T180/Y182), and cotreatment with JNK/SAPK and p38 MAPK inhibitors reduced complexes-induced apoptosis, indicating DNA double-strand break and activation of caspase-mediated apoptosis through JNK/p38 pathways. Complex 1 also reduced HL-60 cell growth in xenograft model. Overall, the outcome indicated the ruthenium(II) complexes with 6-methyl-2-thiouracil as a novel promising antileukemic drug candidates. | 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 | Federal University of Ouro Preto. Department of Chemistry. Ouro Preto, MG, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | 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 Compounds | pt_BR |
| Subject | Leukemia Cell | pt_BR |
| Subject | Cell Proliferation | pt_BR |
| Subject | Humans | pt_BR |
