Tingenone and 22-hydroxytingenone target oxidative stress through downregulation of thioredoxin, leading to DNA double-strand break and JNK/p38-mediated apoptosis in acute myeloid leukemia HL-60 cells
| 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/49165 |
Resumo: | Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) |
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Rodrigues, Ana Carolina Borges da CruzBomfim, Larissa MendesNeves, Sara ParenteSoares, Milena Botelho PereiraDias, Rosane BorgesValverde, Ludmila de FaroRocha, Clarissa Araújo GurgelCosta, Emmanoel VilaçaSilva, Felipe Moura Araujo daGomes, Waldireny RochaKoolen, Hector Henrique FerreiraBezerra, Daniel Pereira2021-09-27T10:30:02Z2021-09-27T10:30:02Z2021RODRIGUES, Ana Carolina Borges da Cruz et al. Tingenone and 22-hydroxytingenone target oxidative stress through downregulation of thioredoxin, leading to DNA double-strand break and JNK/p38-mediated apoptosis in acute myeloid leukemia HL-60 cells. Biomedicine and Pharmacotherapy, v. 142, p. 1-13, 2021.0753-3322https://www.arca.fiocruz.br/handle/icict/4916510.1016/j.biopha.2021.112034Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado do Amazonas (FAPEAM)Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB)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 / Centro Universitário SENAI CIMATEC. Instituto SENAI de Sistemas Avançados de Saúde. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Odontologia. Departamento de Propedêutica e Clínica Integrada. 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. Faculdade de Odontologia. Departamento de Propedêutica e Clínica Integrada. Salvador, BA, Brasil.Universidade Federal do Amazonas. Instituto de Ciências Exatas. Departamento de Química. Manaus, AM, Brasil.Universidade Federal do Amazonas. Instituto de Ciências Exatas. Departamento de Química. Manaus, AM, Brasil.Universidade Federal do Amazonas. Instituto de Saúde e Biotecnologia. Coari, AM, Brasil.Universidade do Estado do Amazonas. Pró-Reitoria de Pesquisa e Pós-Graduação. Grupo de Pesquisa em Metabolômica e Espectrometria de Massas. Manaus, AM, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Acute myeloid leukemia (AML) is the most lethal form of leukemia. Standard anti-AML treatment remains almost unchanged for decades. Tingenone (TG) and 22-hydroxytingenone (22-HTG) are quinonemethide triterpenes found in the Amazonian plant Salacia impressifolia (Celastraceae), with cytotoxic properties in different histological types of cancer cells. In the present work, we investigated the anti-AML action mechanism of TG and 22-HTG in the AML HL-60 cell line. Both compounds exhibited potent cytotoxicity in a panel of cancer cell lines. Mechanistic studies found that TG and 22-HTG reduced cell growth and caused the externalization of phosphatidylserine, the fragmentation of internucleosomal DNA and the loss of mitochondrial transmembrane potential in HL-60 cells. In addition, pre-incubation with Z-VAD(OMe)-FMK, a pan-caspase inhibitor, prevented TGand 22-HTG-induced apoptosis, indicating cell death by apoptosis via a caspase-dependent pathway. The analysis of the RNA transcripts of several genes indicated the interruption of the cellular antioxidant system, including the downregulation of thioredoxin, as a target for TG and 22-HTG. The application of N-acetyl-cysteine, an antioxidant, completely prevented apoptosis induced by TG and 22-HTG, indicating activation of the apoptosis pathway mediated by oxidative stress. Moreover, TG and 22-HTG induced DNA double-strand break and phosphorylation of JNK2 (T183/Y185) and p38α (T180/Y182), and co-incubation with SP 600125 (JNK/SAPK inhibitor) and PD 169316 (p38 MAPK inhibitor) partially prevented apoptosis induced by TG and 22-HTG. Together, these data indicate that TG and 22-HTG are new candidate for anti-AML therapy targeting thioredoxin.engElsevierLeucemia mieloide agudaEstresse oxidativoTioredoxinaCélulas HL-60ApoptoseTingenone22-hydroxytingenoneThioredoxinOxidative stressApoptosisAMLTingenone and 22-hydroxytingenone target oxidative stress through downregulation of thioredoxin, leading to DNA double-strand break and JNK/p38-mediated apoptosis in acute myeloid 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-83097https://www.arca.fiocruz.br/bitstream/icict/49165/1/license.txt36b51ef91c52b5338d9d29ba0cc807bcMD51ORIGINALRodrigues, Ana Carolina B C Tingenone and....pdfRodrigues, Ana Carolina B C Tingenone 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| dc.title.en.fl_str_mv |
Tingenone and 22-hydroxytingenone target oxidative stress through downregulation of thioredoxin, leading to DNA double-strand break and JNK/p38-mediated apoptosis in acute myeloid leukemia HL-60 cells |
| title |
Tingenone and 22-hydroxytingenone target oxidative stress through downregulation of thioredoxin, leading to DNA double-strand break and JNK/p38-mediated apoptosis in acute myeloid leukemia HL-60 cells |
| spellingShingle |
Tingenone and 22-hydroxytingenone target oxidative stress through downregulation of thioredoxin, leading to DNA double-strand break and JNK/p38-mediated apoptosis in acute myeloid leukemia HL-60 cells Rodrigues, Ana Carolina Borges da Cruz Leucemia mieloide aguda Estresse oxidativo Tioredoxina Células HL-60 Apoptose Tingenone 22-hydroxytingenone Thioredoxin Oxidative stress Apoptosis AML |
| title_short |
Tingenone and 22-hydroxytingenone target oxidative stress through downregulation of thioredoxin, leading to DNA double-strand break and JNK/p38-mediated apoptosis in acute myeloid leukemia HL-60 cells |
| title_full |
Tingenone and 22-hydroxytingenone target oxidative stress through downregulation of thioredoxin, leading to DNA double-strand break and JNK/p38-mediated apoptosis in acute myeloid leukemia HL-60 cells |
| title_fullStr |
Tingenone and 22-hydroxytingenone target oxidative stress through downregulation of thioredoxin, leading to DNA double-strand break and JNK/p38-mediated apoptosis in acute myeloid leukemia HL-60 cells |
| title_full_unstemmed |
Tingenone and 22-hydroxytingenone target oxidative stress through downregulation of thioredoxin, leading to DNA double-strand break and JNK/p38-mediated apoptosis in acute myeloid leukemia HL-60 cells |
| title_sort |
Tingenone and 22-hydroxytingenone target oxidative stress through downregulation of thioredoxin, leading to DNA double-strand break and JNK/p38-mediated apoptosis in acute myeloid leukemia HL-60 cells |
| author |
Rodrigues, Ana Carolina Borges da Cruz |
| author_facet |
Rodrigues, Ana Carolina Borges da Cruz Bomfim, Larissa Mendes Neves, Sara Parente Soares, Milena Botelho Pereira Dias, Rosane Borges Valverde, Ludmila de Faro Rocha, Clarissa Araújo Gurgel Costa, Emmanoel Vilaça Silva, Felipe Moura Araujo da Gomes, Waldireny Rocha Koolen, Hector Henrique Ferreira Bezerra, Daniel Pereira |
| author_role |
author |
| author2 |
Bomfim, Larissa Mendes Neves, Sara Parente Soares, Milena Botelho Pereira Dias, Rosane Borges Valverde, Ludmila de Faro Rocha, Clarissa Araújo Gurgel Costa, Emmanoel Vilaça Silva, Felipe Moura Araujo da Gomes, Waldireny Rocha Koolen, Hector Henrique Ferreira Bezerra, Daniel Pereira |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Rodrigues, Ana Carolina Borges da Cruz Bomfim, Larissa Mendes Neves, Sara Parente Soares, Milena Botelho Pereira Dias, Rosane Borges Valverde, Ludmila de Faro Rocha, Clarissa Araújo Gurgel Costa, Emmanoel Vilaça Silva, Felipe Moura Araujo da Gomes, Waldireny Rocha Koolen, Hector Henrique Ferreira Bezerra, Daniel Pereira |
| dc.subject.other.pt_BR.fl_str_mv |
Leucemia mieloide aguda Estresse oxidativo Tioredoxina Células HL-60 Apoptose |
| topic |
Leucemia mieloide aguda Estresse oxidativo Tioredoxina Células HL-60 Apoptose Tingenone 22-hydroxytingenone Thioredoxin Oxidative stress Apoptosis AML |
| dc.subject.en.en.fl_str_mv |
Tingenone 22-hydroxytingenone Thioredoxin Oxidative stress Apoptosis |
| dc.subject.en.pt_BR.fl_str_mv |
AML |
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) |
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2021 |
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2021-09-27T10:30:02Z |
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2021-09-27T10:30:02Z |
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2021 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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RODRIGUES, Ana Carolina Borges da Cruz et al. Tingenone and 22-hydroxytingenone target oxidative stress through downregulation of thioredoxin, leading to DNA double-strand break and JNK/p38-mediated apoptosis in acute myeloid leukemia HL-60 cells. Biomedicine and Pharmacotherapy, v. 142, p. 1-13, 2021. |
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https://www.arca.fiocruz.br/handle/icict/49165 |
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0753-3322 |
| dc.identifier.doi.pt_BR.fl_str_mv |
10.1016/j.biopha.2021.112034 |
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RODRIGUES, Ana Carolina Borges da Cruz et al. Tingenone and 22-hydroxytingenone target oxidative stress through downregulation of thioredoxin, leading to DNA double-strand break and JNK/p38-mediated apoptosis in acute myeloid leukemia HL-60 cells. Biomedicine and Pharmacotherapy, v. 142, p. 1-13, 2021. 0753-3322 10.1016/j.biopha.2021.112034 |
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Elsevier |
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