A novel ruthenium complex with xanthoxylin induces S-phase arrest and causes ERK1/2-mediated apoptosis in HepG2 cells through a p53-independent pathway
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2018 |
| 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/24832 |
Resumo: | Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) |
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Carvalho, Nanashara Coelho deNeves, Sara ParenteDias, Rosane BorgesValverde, Ludmila de FaroSales, Caroline Brandi SchlaepferRocha, Clarissa Araújo GurgelSoares, Milena Botelho PereiraSantos, Edjane Rocha dosOliveira, Regina Maria MendesCarlos, Rose MariaNogueira, Paulo Cesar de LimaBezerra, Daniel Pereira2018-02-15T14:20:03Z2018-02-15T14:20:03Z2018CARVALHO, Nanashara Coelho de et al. A novel ruthenium complex with xanthoxylin induces S-phase arrest and causes ERK1/2-mediated apoptosis in HepG2 cells through a p53-independent pathway. Cell Death and Disease, v. 9, n. 79, p. 2-24, 23 Jan. 2018.2041-4889https://www.arca.fiocruz.br/handle/icict/2483210.1038/s41419-017-0104-6Coordenação 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 São Paulo (FAPESP)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 / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.Universidade Federal de São Carlos. Departamento de Química. São Carlos, SP, Brasil.Universidade Federal de São Carlos. Departamento de Química. São Carlos, SP, Brasil.Universidade Federal de São Carlos. Departamento de Química. São Carlos, SP, Brasil.Universidade Federal de Sergipe. Departamento de Química. São Cristóvão, SE, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Ruthenium-based compounds have gained great interest due to their potent cytotoxicity in cancer cells; however, much of their potential applications remain unexplored. In this paper, we report the synthesis of a novel ruthenium complex with xanthoxylin (RCX) and the investigation of its cellular and molecular action in human hepatocellular carcinoma HepG2 cells. We found that RCX exhibited a potent cytotoxic effect in a panel of cancer cell lines in monolayer cultures and in a 3D model of multicellular cancer spheroids formed from HepG2 cells. This compound is detected at a high concentration in the cell nuclei, induces DNA intercalation and inhibits DNA synthesis, arresting the cell cycle in the S-phase, which is followed by the activation of the caspase-mediated apoptosis pathway in HepG2 cells. Gene expression analysis revealed changes in the expression of genes related to cell cycle control, apoptosis and the MAPK pathway. In addition, RCX induced the phosphorylation of ERK1/2, and pretreatment with U-0126, an MEK inhibitor known to inhibit the activation of ERK1/2, prevented RCX-induced apoptosis. In contrast, pretreatment with a p53 inhibitor (cyclic pifithrin-α) did not prevent RCX-induced apoptosis, indicating the activation of a p53-independent apoptosis pathway. RCX also presented a potent in vivo antitumor effect in C.B-17 SCID mice engrafted with HepG2 cells. Altogether, these results indicate that RCX is a novel anticancer drug candidate.engSpringer NatureCompostos de rutênioCarcinomaAnticorpos antitumoraisHepatocellular carcinomaCiclo celularApoptoseRuthenium complexCarcinomaAntitumor antibodiesCell cycleApoptosisA novel ruthenium complex with xanthoxylin induces S-phase arrest and causes ERK1/2-mediated apoptosis in HepG2 cells through a p53-independent pathwayinfo: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/24832/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALCarvalho NC A novel ruthenium complex with xanthoxylin....pdfCarvalho NC A novel ruthenium complex with xanthoxylin....pdfapplication/pdf9587564https://www.arca.fiocruz.br/bitstream/icict/24832/2/Carvalho%20NC%20A%20novel%20ruthenium%20complex%20with%20xanthoxylin....pdfc4846e72fe08584a4e9a777acbe525bdMD52TEXTCarvalho NC A novel ruthenium complex with xanthoxylin....pdf.txtCarvalho NC A novel ruthenium complex with xanthoxylin....pdf.txtExtracted texttext/plain77706https://www.arca.fiocruz.br/bitstream/icict/24832/3/Carvalho%20NC%20A%20novel%20ruthenium%20complex%20with%20xanthoxylin....pdf.txt44198bd4d10d3b9ef94d91c4640ff2fcMD53icict/248322023-03-15 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| dc.title.en.fl_str_mv |
A novel ruthenium complex with xanthoxylin induces S-phase arrest and causes ERK1/2-mediated apoptosis in HepG2 cells through a p53-independent pathway |
| title |
A novel ruthenium complex with xanthoxylin induces S-phase arrest and causes ERK1/2-mediated apoptosis in HepG2 cells through a p53-independent pathway |
| spellingShingle |
A novel ruthenium complex with xanthoxylin induces S-phase arrest and causes ERK1/2-mediated apoptosis in HepG2 cells through a p53-independent pathway Carvalho, Nanashara Coelho de Compostos de rutênio Carcinoma Anticorpos antitumorais Hepatocellular carcinoma Ciclo celular Apoptose Ruthenium complex Carcinoma Antitumor antibodies Cell cycle Apoptosis |
| title_short |
A novel ruthenium complex with xanthoxylin induces S-phase arrest and causes ERK1/2-mediated apoptosis in HepG2 cells through a p53-independent pathway |
| title_full |
A novel ruthenium complex with xanthoxylin induces S-phase arrest and causes ERK1/2-mediated apoptosis in HepG2 cells through a p53-independent pathway |
| title_fullStr |
A novel ruthenium complex with xanthoxylin induces S-phase arrest and causes ERK1/2-mediated apoptosis in HepG2 cells through a p53-independent pathway |
| title_full_unstemmed |
A novel ruthenium complex with xanthoxylin induces S-phase arrest and causes ERK1/2-mediated apoptosis in HepG2 cells through a p53-independent pathway |
| title_sort |
A novel ruthenium complex with xanthoxylin induces S-phase arrest and causes ERK1/2-mediated apoptosis in HepG2 cells through a p53-independent pathway |
| author |
Carvalho, Nanashara Coelho de |
| author_facet |
Carvalho, Nanashara Coelho de Neves, Sara Parente Dias, Rosane Borges Valverde, Ludmila de Faro Sales, Caroline Brandi Schlaepfer Rocha, Clarissa Araújo Gurgel Soares, Milena Botelho Pereira Santos, Edjane Rocha dos Oliveira, Regina Maria Mendes Carlos, Rose Maria Nogueira, Paulo Cesar de Lima Bezerra, Daniel Pereira |
| author_role |
author |
| author2 |
Neves, Sara Parente Dias, Rosane Borges Valverde, Ludmila de Faro Sales, Caroline Brandi Schlaepfer Rocha, Clarissa Araújo Gurgel Soares, Milena Botelho Pereira Santos, Edjane Rocha dos Oliveira, Regina Maria Mendes Carlos, Rose Maria Nogueira, Paulo Cesar de Lima Bezerra, Daniel Pereira |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Carvalho, Nanashara Coelho de Neves, Sara Parente Dias, Rosane Borges Valverde, Ludmila de Faro Sales, Caroline Brandi Schlaepfer Rocha, Clarissa Araújo Gurgel Soares, Milena Botelho Pereira Santos, Edjane Rocha dos Oliveira, Regina Maria Mendes Carlos, Rose Maria Nogueira, Paulo Cesar de Lima Bezerra, Daniel Pereira |
| dc.subject.other.pt_BR.fl_str_mv |
Compostos de rutênio Carcinoma Anticorpos antitumorais Hepatocellular carcinoma Ciclo celular Apoptose |
| topic |
Compostos de rutênio Carcinoma Anticorpos antitumorais Hepatocellular carcinoma Ciclo celular Apoptose Ruthenium complex Carcinoma Antitumor antibodies Cell cycle Apoptosis |
| dc.subject.en.en.fl_str_mv |
Ruthenium complex Carcinoma Antitumor antibodies Cell cycle Apoptosis |
| description |
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) |
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2018 |
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2018-02-15T14:20:03Z |
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2018-02-15T14:20:03Z |
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2018 |
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info:eu-repo/semantics/article |
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article |
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CARVALHO, Nanashara Coelho de et al. A novel ruthenium complex with xanthoxylin induces S-phase arrest and causes ERK1/2-mediated apoptosis in HepG2 cells through a p53-independent pathway. Cell Death and Disease, v. 9, n. 79, p. 2-24, 23 Jan. 2018. |
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https://www.arca.fiocruz.br/handle/icict/24832 |
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2041-4889 |
| dc.identifier.doi.pt_BR.fl_str_mv |
10.1038/s41419-017-0104-6 |
| identifier_str_mv |
CARVALHO, Nanashara Coelho de et al. A novel ruthenium complex with xanthoxylin induces S-phase arrest and causes ERK1/2-mediated apoptosis in HepG2 cells through a p53-independent pathway. Cell Death and Disease, v. 9, n. 79, p. 2-24, 23 Jan. 2018. 2041-4889 10.1038/s41419-017-0104-6 |
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Springer Nature |
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Springer Nature |
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