A new synthetic antitumor naphthoquinone induces ROS-mediated apoptosis with activation of the JNK and p38 signaling pathways
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| 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/47992 |
Resumo: | Soares, Milena Botelho Pereira; Bezerra, Daniel Pereira. Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. a Laboratory of Biological Activity, Faculty of Pharmaceutical Sciences, Federal University of Amazonas - UFAM, Manaus, Amazonas, 69077-000, Brazil b Laboratory of Pathology and Molecular Biology, Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia, 40296-710, Brazil c Department of Biomorphology, Institute of Health Sciences, Federal University of Bahia - UFBA, Salvador, Bahia, 40110-902, Brazil d Laboratory of Tissue Engineering and Immunopharmacology, Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia, 40296-710, Brazil e Laboratory of Carbohydrate and Nucleotide Synthesis, Department of Organic Chemistry, Federal Fluminense University – UFF, Niter´oi, Rio de Janeiro, 24020-141, Brazil f Laboratory of Signaling in Inflammation, Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Minas Gerais – UFMG, Belo Horizonte, Minas Gerais, 31270-901, Brazil |
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Almeida, Patricia D. O. deJobim, Gleyce dos Santos BarbosaFerreira, Caio César dos SantosBernardes, Lucas RochaDias, Rosane BorgesSales, Caroline Brandi SchlaepferValverde, Ludmila de FaroRocha, Clarissa Araújo GurgelSoares, Milena Botelho PereiraBezerra, Daniel PereiraSilva, Fernando de Carvalho daCardoso, Mariana Filomena do CarmoFerreira, Vitor FranciscoBrito, Larissa F.Sousa, Lirlândia Pires deVasconcellos, Marne C. deLima, Emerson S.2021-07-05T17:26:33Z2021-07-05T17:26:33Z2021ALMEIDA, Patricia D.O. de et al. A new synthetic antitumor naphthoquinone induces ROS-mediated apoptosis with activation of the JNK and p38 signaling pathways. Chemico-Biological Interactions, v. 343, 2021.0009-2797https://www.arca.fiocruz.br/handle/icict/4799210.1016/j.cbi.2021.109444Soares, Milena Botelho Pereira; Bezerra, Daniel Pereira. Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. a Laboratory of Biological Activity, Faculty of Pharmaceutical Sciences, Federal University of Amazonas - UFAM, Manaus, Amazonas, 69077-000, Brazil b Laboratory of Pathology and Molecular Biology, Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia, 40296-710, Brazil c Department of Biomorphology, Institute of Health Sciences, Federal University of Bahia - UFBA, Salvador, Bahia, 40110-902, Brazil d Laboratory of Tissue Engineering and Immunopharmacology, Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia, 40296-710, Brazil e Laboratory of Carbohydrate and Nucleotide Synthesis, Department of Organic Chemistry, Federal Fluminense University – UFF, Niter´oi, Rio de Janeiro, 24020-141, Brazil f Laboratory of Signaling in Inflammation, Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Minas Gerais – UFMG, Belo Horizonte, Minas Gerais, 31270-901, BrazilCNPq, CAPES and FAPEAM for their financial support in the form of grants and fellowship awards. The authors thank to the histotechnology and flow cytometry platforms of FIOCRUZ-Bahia for the performance of histological techniques and flow cytometric data acquisition, respectively. The authors also thank to the Laboratory of Signaling in Inflammation from the Federal University of Minas Gerais (Belo Horizonte, Minas Gerais, Brazil) by technical assistance."Múltipla ver em Notas"Quinones are plant-derived secondary metabolites that present diverse pharmacological properties, including antibacterial, antifungal, antiviral, anti-inflammatory, antipyretic and anticancer activities. In the present study, we evaluated the cytotoxic effect of a new naphthoquinone 6b,7-dihydro-5H-cyclopenta [b]naphtho [2,1-d] furan-5,6 (9aH)-dione) (CNFD) in different tumor cell lines. CNFD displayed cytotoxic activity against different tumor cell lines, especially in MCF-7 human breast adenocarcinoma cells, which showed IC50 values of 3.06 and 0.98 μM for 24 and 48 h incubation, respectively. In wound-healing migration assays, CNFD promoted inhibition of cell migration. We have found typical hallmarks of apoptosis, such as cell shrinkage, chromatin condensation, phosphatidylserine exposure, increase of caspases-9 and-3 activation, increase of internucleosomal DNA fragmentation without affecting the cell membrane permeabilization, increase of ROS production, and loss of mitochondrial membrane potential induced by CNFD. Moreover, gene expression experiments indicated that CNFD increased the expression of the genes CDKN1A, FOS, MAX, and RAC1 and decreased the levels of mRNA transcripts of several genes, including CCND1, CDK2, SOS1, RHOA, GRB2, EGFR and KRAS. The CNFD treatment of MCF-7 cells induced the phosphorylation of c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPKs) and inactivation of extracellular signal-regulated protein kinase 1/2 (ERK1/2). In a study using melanoma cells in a murine model in vivo, CNFD induced a potent anti-tumor activity. Herein, we describe, for the first time, the cytotoxicity and anti-tumor activity of CNFD and sequential mechanisms of apoptosis in MCF-7 cells. CNFD seems to be a promising candidate for anti-tumor therapy.engElsevierNaftoquinonasAdenocarcinomaApoptoseDrogas anticâncerNeoplasiasMamaNaphthoquinoneLawsoneApoptosisAnticancer drugsCarcinogenesisBreast cancerA new synthetic antitumor naphthoquinone induces ROS-mediated apoptosis with activation of the JNK and p38 signaling pathwaysinfo: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-83097https://www.arca.fiocruz.br/bitstream/icict/47992/1/license.txt36b51ef91c52b5338d9d29ba0cc807bcMD51ORIGINALAlmeida, Patricia D.P.de A News syntetic....pdfAlmeida, Patricia D.P.de A News syntetic....pdfapplication/pdf5648951https://www.arca.fiocruz.br/bitstream/icict/47992/2/Almeida%2c%20Patricia%20D.P.de%20A%20News%20syntetic....pdfdb2b599b775fca0aaab4f7862bd9fa79MD52TEXTAlmeida, Patricia 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| dc.title.pt_BR.fl_str_mv |
A new synthetic antitumor naphthoquinone induces ROS-mediated apoptosis with activation of the JNK and p38 signaling pathways |
| title |
A new synthetic antitumor naphthoquinone induces ROS-mediated apoptosis with activation of the JNK and p38 signaling pathways |
| spellingShingle |
A new synthetic antitumor naphthoquinone induces ROS-mediated apoptosis with activation of the JNK and p38 signaling pathways Almeida, Patricia D. O. de Naftoquinonas Adenocarcinoma Apoptose Drogas anticâncer Neoplasias Mama Naphthoquinone Lawsone Apoptosis Anticancer drugs Carcinogenesis Breast cancer |
| title_short |
A new synthetic antitumor naphthoquinone induces ROS-mediated apoptosis with activation of the JNK and p38 signaling pathways |
| title_full |
A new synthetic antitumor naphthoquinone induces ROS-mediated apoptosis with activation of the JNK and p38 signaling pathways |
| title_fullStr |
A new synthetic antitumor naphthoquinone induces ROS-mediated apoptosis with activation of the JNK and p38 signaling pathways |
| title_full_unstemmed |
A new synthetic antitumor naphthoquinone induces ROS-mediated apoptosis with activation of the JNK and p38 signaling pathways |
| title_sort |
A new synthetic antitumor naphthoquinone induces ROS-mediated apoptosis with activation of the JNK and p38 signaling pathways |
| author |
Almeida, Patricia D. O. de |
| author_facet |
Almeida, Patricia D. O. de Jobim, Gleyce dos Santos Barbosa Ferreira, Caio César dos Santos Bernardes, Lucas Rocha Dias, Rosane Borges Sales, Caroline Brandi Schlaepfer Valverde, Ludmila de Faro Rocha, Clarissa Araújo Gurgel Soares, Milena Botelho Pereira Bezerra, Daniel Pereira Silva, Fernando de Carvalho da Cardoso, Mariana Filomena do Carmo Ferreira, Vitor Francisco Brito, Larissa F. Sousa, Lirlândia Pires de Vasconcellos, Marne C. de Lima, Emerson S. |
| author_role |
author |
| author2 |
Jobim, Gleyce dos Santos Barbosa Ferreira, Caio César dos Santos Bernardes, Lucas Rocha Dias, Rosane Borges Sales, Caroline Brandi Schlaepfer Valverde, Ludmila de Faro Rocha, Clarissa Araújo Gurgel Soares, Milena Botelho Pereira Bezerra, Daniel Pereira Silva, Fernando de Carvalho da Cardoso, Mariana Filomena do Carmo Ferreira, Vitor Francisco Brito, Larissa F. Sousa, Lirlândia Pires de Vasconcellos, Marne C. de Lima, Emerson S. |
| author2_role |
author author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Almeida, Patricia D. O. de Jobim, Gleyce dos Santos Barbosa Ferreira, Caio César dos Santos Bernardes, Lucas Rocha Dias, Rosane Borges Sales, Caroline Brandi Schlaepfer Valverde, Ludmila de Faro Rocha, Clarissa Araújo Gurgel Soares, Milena Botelho Pereira Bezerra, Daniel Pereira Silva, Fernando de Carvalho da Cardoso, Mariana Filomena do Carmo Ferreira, Vitor Francisco Brito, Larissa F. Sousa, Lirlândia Pires de Vasconcellos, Marne C. de Lima, Emerson S. |
| dc.subject.other.pt_BR.fl_str_mv |
Naftoquinonas Adenocarcinoma Apoptose Drogas anticâncer Neoplasias Mama |
| topic |
Naftoquinonas Adenocarcinoma Apoptose Drogas anticâncer Neoplasias Mama Naphthoquinone Lawsone Apoptosis Anticancer drugs Carcinogenesis Breast cancer |
| dc.subject.en.pt_BR.fl_str_mv |
Naphthoquinone Lawsone Apoptosis Anticancer drugs Carcinogenesis Breast cancer |
| description |
Soares, Milena Botelho Pereira; Bezerra, Daniel Pereira. Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. a Laboratory of Biological Activity, Faculty of Pharmaceutical Sciences, Federal University of Amazonas - UFAM, Manaus, Amazonas, 69077-000, Brazil b Laboratory of Pathology and Molecular Biology, Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia, 40296-710, Brazil c Department of Biomorphology, Institute of Health Sciences, Federal University of Bahia - UFBA, Salvador, Bahia, 40110-902, Brazil d Laboratory of Tissue Engineering and Immunopharmacology, Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia, 40296-710, Brazil e Laboratory of Carbohydrate and Nucleotide Synthesis, Department of Organic Chemistry, Federal Fluminense University – UFF, Niter´oi, Rio de Janeiro, 24020-141, Brazil f Laboratory of Signaling in Inflammation, Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Minas Gerais – UFMG, Belo Horizonte, Minas Gerais, 31270-901, Brazil |
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2021 |
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2021-07-05T17:26:33Z |
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2021-07-05T17:26:33Z |
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2021 |
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info:eu-repo/semantics/article |
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ALMEIDA, Patricia D.O. de et al. A new synthetic antitumor naphthoquinone induces ROS-mediated apoptosis with activation of the JNK and p38 signaling pathways. Chemico-Biological Interactions, v. 343, 2021. |
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https://www.arca.fiocruz.br/handle/icict/47992 |
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0009-2797 |
| dc.identifier.doi.none.fl_str_mv |
10.1016/j.cbi.2021.109444 |
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ALMEIDA, Patricia D.O. de et al. A new synthetic antitumor naphthoquinone induces ROS-mediated apoptosis with activation of the JNK and p38 signaling pathways. Chemico-Biological Interactions, v. 343, 2021. 0009-2797 10.1016/j.cbi.2021.109444 |
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