A ruthenium-based 5-fluorouracil complex with enhanced cytotoxicity and apoptosis induction action in HCT116 cells

Detalhes bibliográficos
Autor(a) principal: Silva, Valdenizia Rodrigues
Data de Publicação: 2018
Outros Autores: Corrêa, Rodrigo de Sousa, Santos, Luciano de Souza, Soares, Milena Botelho Pereira, Batista, Alzir Azevedo, Bezerra, Daniel Pereira
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
DOI: 10.1038/s41598-017-18639-6
Texto Completo: https://www.arca.fiocruz.br/handle/icict/25642
Resumo: 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), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).
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spelling Silva, Valdenizia RodriguesCorrêa, Rodrigo de SousaSantos, Luciano de SouzaSoares, Milena Botelho PereiraBatista, Alzir AzevedoBezerra, Daniel Pereira2018-04-05T16:59:32Z2018-04-05T16:59:32Z2018SILVA, V. R. et al. A ruthenium-based 5-fluorouracil complex with enhanced cytotoxicity and apoptosis induction action in HCT116 cells. ScientifiC Reports, v. 8, p. 288, 2018.2045-2322https://www.arca.fiocruz.br/handle/icict/2564210.1038/s41598-017-18639-6Coordenação 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), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilFederal University of Ouro Preto. Department of Chemistry. Ouro Preto, MG, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Center of Biotechnology and Cell therapy. Salvador, BA, BrazilFederal University of São Carlos. Department of Chemistry. São Carlos, SP, BrazilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilCombination of multifunctionalities into one compound is a rational strategy in medicinal chemical design, and have often been used with metallodrug-based compounds. In the present study, we synthesized a novel ruthenium-based 5-fluorouracil complex [Ru(5-FU)(PPh3)2(bipy)]PF6(PPh3 = triphenylphosphine; and bipy = 2,2'-bipyridine) with enhanced cytotoxicity in different cancer cells, and assessed its apoptosis induction action in human colon carcinoma HCT116 cells. The complex was characterized by infrared, cyclic voltammetry, molar conductance measurements, elemental analysis, NMR experiments and X-ray crystallographic analysis. In both 2D and 3D cell culture models, the complex presented cytotoxicity to cancer cells more potent than 5-FU. A typical morphology of 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 complex-treated HCT116 cells. Moreover, the pre-treatment with Z-DEVD-FMK, a caspase-3 inhibitor, reduced the apoptosis induced by the complex, indicating cell death by apoptosis through caspase-dependent and mitochondrial intrinsic pathways. The complex failed to induce reactive oxygen species production and DNA intercalation. In conclusion, the novel complex displays enhanced cytotoxicity to different cancer cells, and is able to induce caspase-mediated apoptosis in HCT116 cells.engNature Publishing GroupApoptoseFluorouracilCitotoxicidadeCelulasApoptosisFluorouracilCytotoxicityCellsA ruthenium-based 5-fluorouracil complex with enhanced cytotoxicity and apoptosis induction action in HCT116 cellsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo: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/25642/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALSilva VR A ruthenium-based 5-fluorouracil....pdfSilva VR A ruthenium-based 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dc.title.pt_BR.fl_str_mv A ruthenium-based 5-fluorouracil complex with enhanced cytotoxicity and apoptosis induction action in HCT116 cells
title A ruthenium-based 5-fluorouracil complex with enhanced cytotoxicity and apoptosis induction action in HCT116 cells
spellingShingle A ruthenium-based 5-fluorouracil complex with enhanced cytotoxicity and apoptosis induction action in HCT116 cells
Silva, Valdenizia Rodrigues
Apoptose
Fluorouracil
Citotoxicidade
Celulas
Apoptosis
Fluorouracil
Cytotoxicity
Cells
title_short A ruthenium-based 5-fluorouracil complex with enhanced cytotoxicity and apoptosis induction action in HCT116 cells
title_full A ruthenium-based 5-fluorouracil complex with enhanced cytotoxicity and apoptosis induction action in HCT116 cells
title_fullStr A ruthenium-based 5-fluorouracil complex with enhanced cytotoxicity and apoptosis induction action in HCT116 cells
title_full_unstemmed A ruthenium-based 5-fluorouracil complex with enhanced cytotoxicity and apoptosis induction action in HCT116 cells
title_sort A ruthenium-based 5-fluorouracil complex with enhanced cytotoxicity and apoptosis induction action in HCT116 cells
author Silva, Valdenizia Rodrigues
author_facet Silva, Valdenizia Rodrigues
Corrêa, Rodrigo de Sousa
Santos, Luciano de Souza
Soares, Milena Botelho Pereira
Batista, Alzir Azevedo
Bezerra, Daniel Pereira
author_role author
author2 Corrêa, Rodrigo de Sousa
Santos, Luciano de Souza
Soares, Milena Botelho Pereira
Batista, Alzir Azevedo
Bezerra, Daniel Pereira
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Silva, Valdenizia Rodrigues
Corrêa, Rodrigo de Sousa
Santos, Luciano de Souza
Soares, Milena Botelho Pereira
Batista, Alzir Azevedo
Bezerra, Daniel Pereira
dc.subject.other.pt_BR.fl_str_mv Apoptose
Fluorouracil
Citotoxicidade
Celulas
topic Apoptose
Fluorouracil
Citotoxicidade
Celulas
Apoptosis
Fluorouracil
Cytotoxicity
Cells
dc.subject.en.pt_BR.fl_str_mv Apoptosis
Fluorouracil
Cytotoxicity
Cells
description 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), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).
publishDate 2018
dc.date.accessioned.fl_str_mv 2018-04-05T16:59:32Z
dc.date.available.fl_str_mv 2018-04-05T16:59:32Z
dc.date.issued.fl_str_mv 2018
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv SILVA, V. R. et al. A ruthenium-based 5-fluorouracil complex with enhanced cytotoxicity and apoptosis induction action in HCT116 cells. ScientifiC Reports, v. 8, p. 288, 2018.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/25642
dc.identifier.issn.pt_BR.fl_str_mv 2045-2322
dc.identifier.doi.none.fl_str_mv 10.1038/s41598-017-18639-6
identifier_str_mv SILVA, V. R. et al. A ruthenium-based 5-fluorouracil complex with enhanced cytotoxicity and apoptosis induction action in HCT116 cells. ScientifiC Reports, v. 8, p. 288, 2018.
2045-2322
10.1038/s41598-017-18639-6
url https://www.arca.fiocruz.br/handle/icict/25642
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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