A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 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/31710 |
Resumo: | The authors are grateful to the flow cytometry platform of FIOCRUZ-Bahia for collecting the flow cytometric data. This work received financial support and fellowships from Brazilian agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). In special, we also thank CNPq and CAPES for research fellowships (M.I.F.B.; D.R.M.M.; F.T.M.; R.P.M.; A.C.D; M.B.P.S.; D.P.B.). |
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Oliveira, Maiara de SouzaBarbosa, Marília Imaculada FrazãoSouza, Thiago Belarmino deMoreira, Diogo Rodrigues MagalhãesMartins, Felipe TerraVillarreal, WilmerMachado, Rafael P.Doriguetto, Antônio CarlosSoares, Milena Botelho PereiraBezerra, Daniel Pereira2019-02-18T16:35:02Z2019-02-18T16:35:02Z2019OLIVEIRA, M. S. et al. A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 cells. Redox Biology, v. 20, p. 182–194, 2019.2213-2317https://www.arca.fiocruz.br/handle/icict/3171010.1016/j.redox.2018.10.006The authors are grateful to the flow cytometry platform of FIOCRUZ-Bahia for collecting the flow cytometric data. This work received financial support and fellowships from Brazilian agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). In special, we also thank CNPq and CAPES for research fellowships (M.I.F.B.; D.R.M.M.; F.T.M.; R.P.M.; A.C.D; M.B.P.S.; D.P.B.).Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Federal University of Alfenas. Institute of Chemistry. Alfenas, MG, Brazil.Federal University of Ouro Preto. Department of Pharmacy. Ouro Preto, MG, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Federal University of Goiás. Institute of Chemistry. Goiânia, GO, Brazil.Federal University of São Carlos. Department of Chemistry. São Carlos, SP, Brazil.Federal University of Alfenas. Institute of Chemistry. Alfenas, MG, Brazil.Federal University of Alfenas. Institute of Chemistry. Alfenas, MG, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Piplartine (piperlongumine) is a plant-derived compound found in some Piper species that became a novel potential antineoplastic agent. In the present study, we synthesized a novel platinum complex containing a piplartine derivative cis-[PtCl(PIP-OH)(PPh3)2]PF6 (where, PIP-OH = piplartine demethylated derivative; and PPh3 = triphenylphosphine) with enhanced cytotoxicity in different cancer cells, and investigated its apoptotic action in human promyelocytic leukemia HL-60 cells. The structure of PIP-OH ligand was characterized by X-ray crystallographic analysis and the resulting platinum complex was characterized by infrared, molar conductance measurements, elemental analysis and NMR experiments. We found that the complex is more potent than piplartine in a panel of cancer cell lines. Apoptotic cell morphology, 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 HL-60 cells. Treatment with the complex also caused a marked increase in the production of reactive oxygen species (ROS), and the pretreatment with N-acetyl-L-cysteine, an antioxidant, reduced the complex-induced apoptosis, indicating activation of ROS-mediated apoptosis pathway. Important, pretreatment with a p38 MAPK inhibitor (PD 169316) and MEK inhibitor (U-0126), known to inhibit ERK1/2 activation, also prevented the complex-induced apoptosis. The complex did not induce DNA intercalation in cell-free DNA assays. In conclusion, the complex exhibits more potent cytotoxicity than piplartine in a panel of different cancer cells and triggers ROS/ERK/p38-mediated apoptosis in HL-60 cells.engElsevierPiplartinaPiperlonguminaComplexo de platinaLeucemiaApoptoseROSp38ERKPiplartinePiperlonguminePlatinum complexLeukemiaApoptosisROSp38ERKA novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 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/31710/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALOliveira M.S. A novel platinum complex containing.... 2019.pdfOliveira M.S. 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| dc.title.pt_BR.fl_str_mv |
A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 cells |
| title |
A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 cells |
| spellingShingle |
A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 cells Oliveira, Maiara de Souza Piplartina Piperlongumina Complexo de platina Leucemia Apoptose ROS p38 ERK Piplartine Piperlongumine Platinum complex Leukemia Apoptosis ROS p38 ERK |
| title_short |
A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 cells |
| title_full |
A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 cells |
| title_fullStr |
A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 cells |
| title_full_unstemmed |
A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 cells |
| title_sort |
A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 cells |
| author |
Oliveira, Maiara de Souza |
| author_facet |
Oliveira, Maiara de Souza Barbosa, Marília Imaculada Frazão Souza, Thiago Belarmino de Moreira, Diogo Rodrigues Magalhães Martins, Felipe Terra Villarreal, Wilmer Machado, Rafael P. Doriguetto, Antônio Carlos Soares, Milena Botelho Pereira Bezerra, Daniel Pereira |
| author_role |
author |
| author2 |
Barbosa, Marília Imaculada Frazão Souza, Thiago Belarmino de Moreira, Diogo Rodrigues Magalhães Martins, Felipe Terra Villarreal, Wilmer Machado, Rafael P. Doriguetto, Antônio Carlos Soares, Milena Botelho Pereira Bezerra, Daniel Pereira |
| author2_role |
author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Oliveira, Maiara de Souza Barbosa, Marília Imaculada Frazão Souza, Thiago Belarmino de Moreira, Diogo Rodrigues Magalhães Martins, Felipe Terra Villarreal, Wilmer Machado, Rafael P. Doriguetto, Antônio Carlos Soares, Milena Botelho Pereira Bezerra, Daniel Pereira |
| dc.subject.other.pt_BR.fl_str_mv |
Piplartina Piperlongumina Complexo de platina Leucemia Apoptose ROS p38 ERK |
| topic |
Piplartina Piperlongumina Complexo de platina Leucemia Apoptose ROS p38 ERK Piplartine Piperlongumine Platinum complex Leukemia Apoptosis ROS p38 ERK |
| dc.subject.en.pt_BR.fl_str_mv |
Piplartine Piperlongumine Platinum complex Leukemia Apoptosis ROS p38 ERK |
| description |
The authors are grateful to the flow cytometry platform of FIOCRUZ-Bahia for collecting the flow cytometric data. This work received financial support and fellowships from Brazilian agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). In special, we also thank CNPq and CAPES for research fellowships (M.I.F.B.; D.R.M.M.; F.T.M.; R.P.M.; A.C.D; M.B.P.S.; D.P.B.). |
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2019 |
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2019-02-18T16:35:02Z |
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2019-02-18T16:35:02Z |
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2019 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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OLIVEIRA, M. S. et al. A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 cells. Redox Biology, v. 20, p. 182–194, 2019. |
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https://www.arca.fiocruz.br/handle/icict/31710 |
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2213-2317 |
| dc.identifier.doi.none.fl_str_mv |
10.1016/j.redox.2018.10.006 |
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OLIVEIRA, M. S. et al. A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 cells. Redox Biology, v. 20, p. 182–194, 2019. 2213-2317 10.1016/j.redox.2018.10.006 |
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Elsevier |
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Elsevier |
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