Novel piplartine-containing ruthenium complexes: synthesis, cell growth inhibition, apoptosis induction and ROS production on HCT116 cells
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2017 |
| 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/24848 |
Resumo: | Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) |
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Costa, Cinara Oliveira D'SousaAraujo Neto, João HonoratoBaliza, Ingrid Rayssa SouzaDias, Rosane BorgesValverde, Ludmila de FaroVidal, Manuela Torres AndionSales, Caroline Brandi SchlaepferRocha, Clarissa Araújo GurgelMoreira, Diogo Rodrigo MagalhãesSoares, Milena Botelho PereiraBatista, Alzir AzevedoBezerra, Daniel Pereira2018-02-15T16:55:43Z2018-02-15T16:55:43Z2017COSTA, Cinara Oliveira D'Sousa et al. Novel piplartine-containing ruthenium complexes: synthesis, cell growth inhibition, apoptosis induction and ROS production on HCT116 cells. Oncotarget, v. 8, n. 61, p. 104367-104392, 1 Nov. 2017.1949-2553https://www.arca.fiocruz.br/handle/icict/2484810.18632/oncotarget.222481949-2553Coordenação 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 São Paulo (FAPESP)Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Universidade Federal de São Carlos. Departamento de Química. São Carlos, SP, Brasil.Fundação 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.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Universidade Federal da Bahia. Instituto de Ciências da Saúde. Departamento de Biomorfologia. Salvador, BA, Brasil.Fundação 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 / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.Universidade Federal de São Carlos. Departamento de Química. São Carlos, SP, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Piplartine (piperlongumine) is a plant-derived molecule that has been receiving intense interest due to its anticancer characteristics that target the oxidative stress. In the present paper, two novel piplartine-containing ruthenium complexes [Ru(piplartine)(dppf)(bipy)](PF6)2(1) and [Ru(piplartine)(dppb)(bipy)](PF6)2(2) were synthesized and investigated for their cellular and molecular responses on cancer cell lines. We found that both complexes are more potent than metal-free piplartine in a panel of cancer cell lines on monolayer cultures, as well in 3D model of cancer multicellular spheroids formed from human colon carcinoma HCT116 cells. Mechanistic studies uncovered that the complexes reduced the cell growth and caused phosphatidylserine externalization, internucleosomal DNA fragmentation, caspase-3 activation and loss of the mitochondrial transmembrane potential on HCT116 cells. Moreover, the pre-treatment with Z-VAD(OMe)-FMK, a pan-caspase inhibitor, reduced the complexes-induced apoptosis, indicating cell death by apoptosis through caspase-dependent and mitochondrial intrinsic pathways. Treatment with the complexes also caused a marked increase in the production of reactive oxygen species (ROS), including hydrogen peroxide, superoxide anion and nitric oxide, and decreased reduced glutathione levels. Application of N-acetyl-cysteine, an antioxidant, reduced the ROS levels and apoptosis induced by the complexes, indicating activation of ROS-mediated apoptosis pathway. RNA transcripts of several genes, including gene related to the cell cycle, apoptosis and oxidative stress, were regulated under treatment. However, the complexes failed to induce DNA intercalation. In conclusion, the complexes are more potent than piplartine against different cancer cell lines and are able to induce caspase-dependent and mitochondrial intrinsic apoptosis on HCT116 cells by ROS-mediated pathway.engImpact JournalsPiplartinaPiperlonguminaComplexos de rutênioROSApoptosePiplartinePiperlongumineRuthenium complexesROSApoptosisNovel piplartine-containing ruthenium complexes: synthesis, cell growth inhibition, apoptosis induction and ROS production on 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/24848/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALCosta CO Novel piplartine-containing ruthenium .....pdfCosta CO Novel piplartine-containing ruthenium 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| dc.title.en.fl_str_mv |
Novel piplartine-containing ruthenium complexes: synthesis, cell growth inhibition, apoptosis induction and ROS production on HCT116 cells |
| title |
Novel piplartine-containing ruthenium complexes: synthesis, cell growth inhibition, apoptosis induction and ROS production on HCT116 cells |
| spellingShingle |
Novel piplartine-containing ruthenium complexes: synthesis, cell growth inhibition, apoptosis induction and ROS production on HCT116 cells Costa, Cinara Oliveira D'Sousa Piplartina Piperlongumina Complexos de rutênio ROS Apoptose Piplartine Piperlongumine Ruthenium complexes ROS Apoptosis |
| title_short |
Novel piplartine-containing ruthenium complexes: synthesis, cell growth inhibition, apoptosis induction and ROS production on HCT116 cells |
| title_full |
Novel piplartine-containing ruthenium complexes: synthesis, cell growth inhibition, apoptosis induction and ROS production on HCT116 cells |
| title_fullStr |
Novel piplartine-containing ruthenium complexes: synthesis, cell growth inhibition, apoptosis induction and ROS production on HCT116 cells |
| title_full_unstemmed |
Novel piplartine-containing ruthenium complexes: synthesis, cell growth inhibition, apoptosis induction and ROS production on HCT116 cells |
| title_sort |
Novel piplartine-containing ruthenium complexes: synthesis, cell growth inhibition, apoptosis induction and ROS production on HCT116 cells |
| author |
Costa, Cinara Oliveira D'Sousa |
| author_facet |
Costa, Cinara Oliveira D'Sousa Araujo Neto, João Honorato Baliza, Ingrid Rayssa Souza Dias, Rosane Borges Valverde, Ludmila de Faro Vidal, Manuela Torres Andion Sales, Caroline Brandi Schlaepfer Rocha, Clarissa Araújo Gurgel Moreira, Diogo Rodrigo Magalhães Soares, Milena Botelho Pereira Batista, Alzir Azevedo Bezerra, Daniel Pereira |
| author_role |
author |
| author2 |
Araujo Neto, João Honorato Baliza, Ingrid Rayssa Souza Dias, Rosane Borges Valverde, Ludmila de Faro Vidal, Manuela Torres Andion Sales, Caroline Brandi Schlaepfer Rocha, Clarissa Araújo Gurgel Moreira, Diogo Rodrigo Magalhães Soares, Milena Botelho Pereira Batista, Alzir Azevedo Bezerra, Daniel Pereira |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Costa, Cinara Oliveira D'Sousa Araujo Neto, João Honorato Baliza, Ingrid Rayssa Souza Dias, Rosane Borges Valverde, Ludmila de Faro Vidal, Manuela Torres Andion Sales, Caroline Brandi Schlaepfer Rocha, Clarissa Araújo Gurgel Moreira, Diogo Rodrigo Magalhães Soares, Milena Botelho Pereira Batista, Alzir Azevedo Bezerra, Daniel Pereira |
| dc.subject.other.pt_BR.fl_str_mv |
Piplartina Piperlongumina Complexos de rutênio ROS Apoptose |
| topic |
Piplartina Piperlongumina Complexos de rutênio ROS Apoptose Piplartine Piperlongumine Ruthenium complexes ROS Apoptosis |
| dc.subject.en.en.fl_str_mv |
Piplartine Piperlongumine Ruthenium complexes ROS Apoptosis |
| description |
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) |
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2017 |
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2017 |
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2018-02-15T16:55:43Z |
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2018-02-15T16:55:43Z |
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info:eu-repo/semantics/article |
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article |
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COSTA, Cinara Oliveira D'Sousa et al. Novel piplartine-containing ruthenium complexes: synthesis, cell growth inhibition, apoptosis induction and ROS production on HCT116 cells. Oncotarget, v. 8, n. 61, p. 104367-104392, 1 Nov. 2017. |
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https://www.arca.fiocruz.br/handle/icict/24848 |
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1949-2553 |
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10.18632/oncotarget.22248 |
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1949-2553 |
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COSTA, Cinara Oliveira D'Sousa et al. Novel piplartine-containing ruthenium complexes: synthesis, cell growth inhibition, apoptosis induction and ROS production on HCT116 cells. Oncotarget, v. 8, n. 61, p. 104367-104392, 1 Nov. 2017. 1949-2553 10.18632/oncotarget.22248 |
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