Avaliação dos efeitos anticancerígenos dos 1,2,3-triazóis derivados do núcleo 1,4-naftoquinona em linhagens leucêmicas humanas
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFPB |
Texto Completo: | https://repositorio.ufpb.br/jspui/handle/tede/6816 |
Resumo: | The triazole nucleus and its derivatives have attracted considerable attention in recent decades for their chemotherapeutic potentials. Specifically, the interest in molecules containing the 1,2,3-triazole as chemotherapeutic agents for various diseases has increased, because they are known to exhibit a wide range of biological activities, such as anti-proliferative and anti-neoplastic. The aim of this study was to evaluate the potencial anti-cancer effect of new triazole derivatives from 1,4-naphthoquinone, elucidating their cytotoxicity and cell death mechanisms involved. From five cancer cell lines tested, leukemic cells (HL-60 and K562) were the most sensitive, and between the eight triazole compounds tested (called C1 to C8), compounds C2 and C3 showed the best IC50 of 14 μM and 41 μM for HL-60 cells and 24 μM and 81 μM for K562 cells, respectively. However, these two compounds showed very little cytotoxic effect towards PBMC normal cells with IC50 superior to 80 μM. Investigating the type of cell death induced by compounds C2 and C3, it was showed that compounds induced apoptosis in HL-60 cells and cell cycle arrest in the S-phase, and necrosis in K562 ones. Cell cycle arrest in S phase was related to the expression of the p21 gene in K562. Results revealed a reduced expression of Bcl-2 protein and an increased expression of BAX protein in HL-60 cells. Moreover, it was found cytochrome c release, suggesting involvement of the intrinsic pathway in apoptosis induction in these cells. Activation of this pathway may be through inhibition of ERK phosphorylation. Our results also showed that pre-treatment of HL-60 cells with N-acetyl cysteine (1 mM) for 1 hour reduced the cytotoxic effect of compounds C2 and C3 for 30,83% and 26,47% respectively; indicating that the induction of apoptosis in HL-60 is mediated by increased production of intracellular ROS. Thus, it can be concluded that C2 and C3 compounds showed cytotoxic effects on HL-60 and K562 cells, so, can be considered as prototype anti-leukemic molecules. |
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Avaliação dos efeitos anticancerígenos dos 1,2,3-triazóis derivados do núcleo 1,4-naftoquinona em linhagens leucêmicas humanasEvaluation of anticancer effects of 1,2,3-triazoles derivates to the nucleus 1,4-naphthoquinone in human leukemic cell lines.ApoptoseCiclo celularCitotoxicidadeCitometria de fluxoEROSLeucemia mielóide1,2,3-triazol-1,4-naftoquinonasApoptosisCell cycleCytotoxicityFlow cytometryMyeloid leukemiaROS1,2,3-triazole-1,4-naphthoquinonesCIENCIAS BIOLOGICAS::FARMACOLOGIAThe triazole nucleus and its derivatives have attracted considerable attention in recent decades for their chemotherapeutic potentials. Specifically, the interest in molecules containing the 1,2,3-triazole as chemotherapeutic agents for various diseases has increased, because they are known to exhibit a wide range of biological activities, such as anti-proliferative and anti-neoplastic. The aim of this study was to evaluate the potencial anti-cancer effect of new triazole derivatives from 1,4-naphthoquinone, elucidating their cytotoxicity and cell death mechanisms involved. From five cancer cell lines tested, leukemic cells (HL-60 and K562) were the most sensitive, and between the eight triazole compounds tested (called C1 to C8), compounds C2 and C3 showed the best IC50 of 14 μM and 41 μM for HL-60 cells and 24 μM and 81 μM for K562 cells, respectively. However, these two compounds showed very little cytotoxic effect towards PBMC normal cells with IC50 superior to 80 μM. Investigating the type of cell death induced by compounds C2 and C3, it was showed that compounds induced apoptosis in HL-60 cells and cell cycle arrest in the S-phase, and necrosis in K562 ones. Cell cycle arrest in S phase was related to the expression of the p21 gene in K562. Results revealed a reduced expression of Bcl-2 protein and an increased expression of BAX protein in HL-60 cells. Moreover, it was found cytochrome c release, suggesting involvement of the intrinsic pathway in apoptosis induction in these cells. Activation of this pathway may be through inhibition of ERK phosphorylation. Our results also showed that pre-treatment of HL-60 cells with N-acetyl cysteine (1 mM) for 1 hour reduced the cytotoxic effect of compounds C2 and C3 for 30,83% and 26,47% respectively; indicating that the induction of apoptosis in HL-60 is mediated by increased production of intracellular ROS. Thus, it can be concluded that C2 and C3 compounds showed cytotoxic effects on HL-60 and K562 cells, so, can be considered as prototype anti-leukemic molecules.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESO núcleo triazol e seus derivados têm atraído uma atenção considerável nessas últimas décadas devido ao seu potencial quimioterápico. Mais especificamente, tem se verificado o interesse em moléculas que contêm o grupo 1,2,3-triazol, isto porque esta classe de heterocíclicos é conhecida por exibir uma vasta gama de atividades biológicas, tais como, anti-proliferativo e anti-neoplásico. O objetivo desse trabalho foi o de avaliar o potencial anticancerígeno de novos triazóis derivados do 1,4-naftoquinona, elucidando as suas citotoxicidades e o mecanismo de morte envolvido. Os resultados obtidos revelaram que, das cinco linhagens cancerígenas testadas, as linhagens leucêmicas HL-60 e K562 foram as mais sensíveis, e dentre os oito compostos (denominados C1 a C8) testados, C2 e C3 foram os mais citotóxicos, apresentando CI50 de 14 μM e 41 μM, em HL-60 e de 24 μM e 81 μM em K562, respectivamente. Entretanto, os compostos foram menos citotóxicos nas células normais do sangue periférico humano com CI50 acima 80 μM. Investigando o tipo de morte induzido pelos compostos nas duas linhagens, foi demonstrado que os compostos C2 e C3 induziram apoptose em HL-60. Já nas células K562, este dois derivados provocaram a parada do ciclo celular na fase S e necrose. A parada do ciclo celular na fase S em K562 foi relacionada com a expressão do gene p21. Foi revelado a diminuição da expressão da proteína Bcl-2 e o aumento da expressão da proteína BAX nas células HL-60, e ainda verificou-se a liberação do citocromo c sugerindo a participação da via intrínseca na indução da apoptose em HL-60. A ativação dessa via pode ser via inibição da fosforilação da proteína ERK. Os resultados mostraram também que durante uma hora de pré-tratamento das células HL-60 com o N-acetil cisteina (1 mM), houve a redução da citotoxicidade dos compostos C2 e C3 de 30,83% e 26,47% respectivamente; indicando que a indução da apoptose em HL-60 é mediada pelo aumento da produção das espécies reativas de oxigênio intracelulares. Dessa forma, pode-se concluir que os compostos C2 e C3 apresentaram efeitos citotóxicos frente às linhagens HL-60 e K562, então, podem ser considerados como protótipo de moléculas anti-leucêmicas.Universidade Federal da ParaíbaBRFarmacologiaPrograma de Pós-Graduação em Produtos Naturais e Sintéticos BioativosUFPBAraújo, Demétrius Antonio Machado dehttp://lattes.cnpq.br/4795833304329411Oliveira, Eduardo de Jesushttp://lattes.cnpq.br/1293090609428232Coulidiati, Tangbadioa Herve2015-05-14T13:00:01Z2018-07-21T00:25:18Z2014-10-222018-07-21T00:25:18Z2014-09-18info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfCOULIDIATI, Tangbadioa Herve. Avaliação dos efeitos anticancerígenos dos 1,2,3-triazóis derivados do núcleo 1,4-naftoquinona em linhagens leucêmicas humanas. 2014. 131 f. Tese (Doutorado em Produtos Naturais e Sintéticos Bioativos) - Universidade Federal da Paraíba, João Pessoa, 2014.https://repositorio.ufpb.br/jspui/handle/tede/6816porinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2018-09-06T02:03:01Zoai:repositorio.ufpb.br:tede/6816Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2018-09-06T02:03:01Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false |
dc.title.none.fl_str_mv |
Avaliação dos efeitos anticancerígenos dos 1,2,3-triazóis derivados do núcleo 1,4-naftoquinona em linhagens leucêmicas humanas Evaluation of anticancer effects of 1,2,3-triazoles derivates to the nucleus 1,4-naphthoquinone in human leukemic cell lines. |
title |
Avaliação dos efeitos anticancerígenos dos 1,2,3-triazóis derivados do núcleo 1,4-naftoquinona em linhagens leucêmicas humanas |
spellingShingle |
Avaliação dos efeitos anticancerígenos dos 1,2,3-triazóis derivados do núcleo 1,4-naftoquinona em linhagens leucêmicas humanas Coulidiati, Tangbadioa Herve Apoptose Ciclo celular Citotoxicidade Citometria de fluxo EROS Leucemia mielóide 1,2,3-triazol-1,4-naftoquinonas Apoptosis Cell cycle Cytotoxicity Flow cytometry Myeloid leukemia ROS 1,2,3-triazole-1,4-naphthoquinones CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Avaliação dos efeitos anticancerígenos dos 1,2,3-triazóis derivados do núcleo 1,4-naftoquinona em linhagens leucêmicas humanas |
title_full |
Avaliação dos efeitos anticancerígenos dos 1,2,3-triazóis derivados do núcleo 1,4-naftoquinona em linhagens leucêmicas humanas |
title_fullStr |
Avaliação dos efeitos anticancerígenos dos 1,2,3-triazóis derivados do núcleo 1,4-naftoquinona em linhagens leucêmicas humanas |
title_full_unstemmed |
Avaliação dos efeitos anticancerígenos dos 1,2,3-triazóis derivados do núcleo 1,4-naftoquinona em linhagens leucêmicas humanas |
title_sort |
Avaliação dos efeitos anticancerígenos dos 1,2,3-triazóis derivados do núcleo 1,4-naftoquinona em linhagens leucêmicas humanas |
author |
Coulidiati, Tangbadioa Herve |
author_facet |
Coulidiati, Tangbadioa Herve |
author_role |
author |
dc.contributor.none.fl_str_mv |
Araújo, Demétrius Antonio Machado de http://lattes.cnpq.br/4795833304329411 Oliveira, Eduardo de Jesus http://lattes.cnpq.br/1293090609428232 |
dc.contributor.author.fl_str_mv |
Coulidiati, Tangbadioa Herve |
dc.subject.por.fl_str_mv |
Apoptose Ciclo celular Citotoxicidade Citometria de fluxo EROS Leucemia mielóide 1,2,3-triazol-1,4-naftoquinonas Apoptosis Cell cycle Cytotoxicity Flow cytometry Myeloid leukemia ROS 1,2,3-triazole-1,4-naphthoquinones CIENCIAS BIOLOGICAS::FARMACOLOGIA |
topic |
Apoptose Ciclo celular Citotoxicidade Citometria de fluxo EROS Leucemia mielóide 1,2,3-triazol-1,4-naftoquinonas Apoptosis Cell cycle Cytotoxicity Flow cytometry Myeloid leukemia ROS 1,2,3-triazole-1,4-naphthoquinones CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
The triazole nucleus and its derivatives have attracted considerable attention in recent decades for their chemotherapeutic potentials. Specifically, the interest in molecules containing the 1,2,3-triazole as chemotherapeutic agents for various diseases has increased, because they are known to exhibit a wide range of biological activities, such as anti-proliferative and anti-neoplastic. The aim of this study was to evaluate the potencial anti-cancer effect of new triazole derivatives from 1,4-naphthoquinone, elucidating their cytotoxicity and cell death mechanisms involved. From five cancer cell lines tested, leukemic cells (HL-60 and K562) were the most sensitive, and between the eight triazole compounds tested (called C1 to C8), compounds C2 and C3 showed the best IC50 of 14 μM and 41 μM for HL-60 cells and 24 μM and 81 μM for K562 cells, respectively. However, these two compounds showed very little cytotoxic effect towards PBMC normal cells with IC50 superior to 80 μM. Investigating the type of cell death induced by compounds C2 and C3, it was showed that compounds induced apoptosis in HL-60 cells and cell cycle arrest in the S-phase, and necrosis in K562 ones. Cell cycle arrest in S phase was related to the expression of the p21 gene in K562. Results revealed a reduced expression of Bcl-2 protein and an increased expression of BAX protein in HL-60 cells. Moreover, it was found cytochrome c release, suggesting involvement of the intrinsic pathway in apoptosis induction in these cells. Activation of this pathway may be through inhibition of ERK phosphorylation. Our results also showed that pre-treatment of HL-60 cells with N-acetyl cysteine (1 mM) for 1 hour reduced the cytotoxic effect of compounds C2 and C3 for 30,83% and 26,47% respectively; indicating that the induction of apoptosis in HL-60 is mediated by increased production of intracellular ROS. Thus, it can be concluded that C2 and C3 compounds showed cytotoxic effects on HL-60 and K562 cells, so, can be considered as prototype anti-leukemic molecules. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-10-22 2014-09-18 2015-05-14T13:00:01Z 2018-07-21T00:25:18Z 2018-07-21T00:25:18Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
COULIDIATI, Tangbadioa Herve. Avaliação dos efeitos anticancerígenos dos 1,2,3-triazóis derivados do núcleo 1,4-naftoquinona em linhagens leucêmicas humanas. 2014. 131 f. Tese (Doutorado em Produtos Naturais e Sintéticos Bioativos) - Universidade Federal da Paraíba, João Pessoa, 2014. https://repositorio.ufpb.br/jspui/handle/tede/6816 |
identifier_str_mv |
COULIDIATI, Tangbadioa Herve. Avaliação dos efeitos anticancerígenos dos 1,2,3-triazóis derivados do núcleo 1,4-naftoquinona em linhagens leucêmicas humanas. 2014. 131 f. Tese (Doutorado em Produtos Naturais e Sintéticos Bioativos) - Universidade Federal da Paraíba, João Pessoa, 2014. |
url |
https://repositorio.ufpb.br/jspui/handle/tede/6816 |
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por |
language |
por |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Universidade Federal da Paraíba BR Farmacologia Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos UFPB |
publisher.none.fl_str_mv |
Universidade Federal da Paraíba BR Farmacologia Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos UFPB |
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Biblioteca Digital de Teses e Dissertações da UFPB |
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Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB) |
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