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
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2019 |
| Outros Autores: | , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/36263 |
Resumo: | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. |
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Bomfim, Larissa MendesAraujo, Fênix A. deDias, Rosane BorgesSales, Caroline Brandi SchlaepferRocha, Clarissa Araújo GurgelCorrea, Rodrigo de SousaSoares, Milena Botelho PereiraBatista, Alzir AzevedoBezerra, Daniel Pereira2019-10-08T14:32:30Z2019-10-08T14:32:30Z2019BOMFIM, 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, 2019.2045-2322https://www.arca.fiocruz.br/handle/icict/3626310.1038/s41598-019-47914-xengNature ResearchCompostos de RutênioLeucemia de CélulasProliferação CelularHumanosRuthenium CompoundsLeukemia CellCell ProliferationHumansRuthenium(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 cellsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Federal University of Bahia. Institute of Health Sciences. Department of Biomorphology. Salvador, BA, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Federal University of Ouro Preto. Department of Chemistry. Ouro Preto, MG, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Federal University of São Carlos. Department of Chemistry. São Carlos, SP, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.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.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/36263/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALBomfim M, l. Ruthenium (II).pdfBomfim M, l. Ruthenium (II).pdfapplication/pdf5950873https://www.arca.fiocruz.br/bitstream/icict/36263/2/Bomfim%20M%2c%20l.%20Ruthenium%20%28II%29.pdf69b76d29b685a484dd9c71691535be5eMD52TEXTBomfim M, l. Ruthenium (II).pdf.txtBomfim M, l. 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| dc.title.pt_BR.fl_str_mv |
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 |
| 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 |
| spellingShingle |
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 Bomfim, Larissa Mendes Compostos de Rutênio Leucemia de Células Proliferação Celular Humanos Ruthenium Compounds Leukemia Cell Cell Proliferation Humans |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| author |
Bomfim, Larissa Mendes |
| author_facet |
Bomfim, Larissa Mendes Araujo, Fênix A. de Dias, Rosane Borges Sales, Caroline Brandi Schlaepfer Rocha, Clarissa Araújo Gurgel Correa, Rodrigo de Sousa Soares, Milena Botelho Pereira Batista, Alzir Azevedo Bezerra, Daniel Pereira |
| author_role |
author |
| author2 |
Araujo, Fênix A. de Dias, Rosane Borges Sales, Caroline Brandi Schlaepfer Rocha, Clarissa Araújo Gurgel Correa, Rodrigo de Sousa Soares, Milena Botelho Pereira Batista, Alzir Azevedo Bezerra, Daniel Pereira |
| author2_role |
author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Bomfim, Larissa Mendes Araujo, Fênix A. de Dias, Rosane Borges Sales, Caroline Brandi Schlaepfer Rocha, Clarissa Araújo Gurgel Correa, Rodrigo de Sousa Soares, Milena Botelho Pereira Batista, Alzir Azevedo Bezerra, Daniel Pereira |
| dc.subject.other.pt_BR.fl_str_mv |
Compostos de Rutênio Leucemia de Células Proliferação Celular Humanos |
| topic |
Compostos de Rutênio Leucemia de Células Proliferação Celular Humanos Ruthenium Compounds Leukemia Cell Cell Proliferation Humans |
| dc.subject.en.pt_BR.fl_str_mv |
Ruthenium Compounds Leukemia Cell Cell Proliferation Humans |
| description |
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. |
| publishDate |
2019 |
| dc.date.accessioned.fl_str_mv |
2019-10-08T14:32:30Z |
| dc.date.available.fl_str_mv |
2019-10-08T14:32:30Z |
| dc.date.issued.fl_str_mv |
2019 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.citation.fl_str_mv |
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. |
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https://www.arca.fiocruz.br/handle/icict/36263 |
| dc.identifier.issn.pt_BR.fl_str_mv |
2045-2322 |
| dc.identifier.doi.none.fl_str_mv |
10.1038/s41598-019-47914-x |
| identifier_str_mv |
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. 2045-2322 10.1038/s41598-019-47914-x |
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Nature Research |
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Nature Research |
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