Avaliação da atividade antileucêmica in vitro e toxicológica in vivo do composto LQFM-018
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFG |
Texto Completo: | http://repositorio.bc.ufg.br/tede/handle/tede/7426 |
Resumo: | Cancer is a serious public health problem not only in Brazil but worldwide. Among the various types of cancer known, leukemia is a one of high incidence. In this context, our study aimed to verify the citotoxicity of the compound LQFM-018, in leukemic cells. Both the method of trypan blue exclusion as in the MTT, it was observed a concentration and time dependent response after treatment with the compound LQFM-018. The cell death mechanism was assessed by flow cytometry. The cell cycle analysis showed a decrease of cells in G1 phase with a consequent increase in S phase and G2 / M. The cell death mechanism detected by annexin-V test showed that the K-562 cells were mainly in necrosis. The increased release of LDH also corroborated with the necrotic process. In the treated cells, there was not a significant expression of tumor suppressor protein p-53. The expression of nuclear factor кB increased and decreased expression of ROS. It was also found an increased expression of TNF-R1 receptor, cytochrome-c, decreased ΔΨm and not the expression of proteins Bax and Bcl-2. Acute oral toxicity test was done in vivo. According to the results, the compound LQFM-018 was classified as category 5. The statistical analysis was done using Student t test and ANOVA followed or not by Bonferroni post-test. Was considered statistically significant p<0.05. From these results, we found that the compound LQFM-018 presents potential antitumor activity, but other tests are needed to confirm these results. |
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Bozinis, Marize Campos Valadareshttp://lattes.cnpq.br/6157755243167018Bozinis, Marize Campos Valadareshttp://lattes.cnpq.br/6157755243167018Blanco, Marcos LuengoCruz, Andrezza Furquim dahttp://lattes.cnpq.br/2473157789367544Costa, Fabiana Bettanin2017-06-07T12:26:50Z2011-08-31COSTA, F. B. Avaliação da atividade antileucêmica in vitro e toxicológica in vivo do composto LQFM-018. 2011. 110 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2011.http://repositorio.bc.ufg.br/tede/handle/tede/7426Cancer is a serious public health problem not only in Brazil but worldwide. Among the various types of cancer known, leukemia is a one of high incidence. In this context, our study aimed to verify the citotoxicity of the compound LQFM-018, in leukemic cells. Both the method of trypan blue exclusion as in the MTT, it was observed a concentration and time dependent response after treatment with the compound LQFM-018. The cell death mechanism was assessed by flow cytometry. The cell cycle analysis showed a decrease of cells in G1 phase with a consequent increase in S phase and G2 / M. The cell death mechanism detected by annexin-V test showed that the K-562 cells were mainly in necrosis. The increased release of LDH also corroborated with the necrotic process. In the treated cells, there was not a significant expression of tumor suppressor protein p-53. The expression of nuclear factor кB increased and decreased expression of ROS. It was also found an increased expression of TNF-R1 receptor, cytochrome-c, decreased ΔΨm and not the expression of proteins Bax and Bcl-2. Acute oral toxicity test was done in vivo. According to the results, the compound LQFM-018 was classified as category 5. The statistical analysis was done using Student t test and ANOVA followed or not by Bonferroni post-test. Was considered statistically significant p<0.05. From these results, we found that the compound LQFM-018 presents potential antitumor activity, but other tests are needed to confirm these results.O câncer consiste em um grave problema de saúde pública, não só no Brasil, mas em todo mundo. Dentre os diversos tipos de câncer conhecidos, temos a leucemia, um tipo de neoplasia que vêm apresentando alta incidência. Neste contexto, nossos estudos objetivaram avaliar a atividade antitumoral do composto LQFM-018, em linhagem leucêmica. A investigação do potencial citotóxico foi realizada usando dois métodos in vitro: o MTT e o método de exclusão do azul de tripano. Tanto no método de exclusão do azul de tripano como no MTT, foi observado uma resposta concentração e tempo dependente após tratamento com o composto LQFM-018. Também foi avaliado o mecanismo de morte celular por citometria de fluxo. A análise do ciclo celular mostrou uma diminuição de células na fase G1 com consequente aumento na fase S e G2/M. A avaliação do mecanismo de morte celular pelo teste de anexina-V mostrou que as células K-562 encontram-se principalmente em necrose. O aumento de LDH liberado também corrobora com o processo necrótico. Nas células tratadas, não foi encontrada expressão significativa da proteína supressora de tumor p-53. Já a expressão do fator nuclear кB mostrou-se aumentada. Foi também encontrado um aumento na expressão do receptor TNF-R1, do citocromo-c, diminuição do ΔΨm e do ROS e não expressão das proteínas Bax e BcL-2. Como ensaio de segurança in vivo foi feito o teste de toxicidade oral aguda. Nesse ensaio, a substância teste foi classificada como pertencente à categoria 5. A estatística foi feita usando teste t e ANOVA seguido ou não do pós-teste de Bonferroni. Foi considerado estatisticamente significativo p<0,05. A partir desses resultados, observamos que a molécula LQFM-018 apresenta potencial antitumoral, porém outros ensaios são necessários para confirmação desses resultados.Submitted by JÚLIO HEBER SILVA (julioheber@yahoo.com.br) on 2017-06-06T20:05:41Z No. of bitstreams: 2 Dissertação - Fabiana Bettanin Costa - 2011.pdf: 2024050 bytes, checksum: 3173344e4dab4039f2966cebdd1a98fc (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-06-07T12:26:50Z (GMT) No. of bitstreams: 2 Dissertação - Fabiana Bettanin Costa - 2011.pdf: 2024050 bytes, checksum: 3173344e4dab4039f2966cebdd1a98fc (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2017-06-07T12:26:50Z (GMT). No. of bitstreams: 2 Dissertação - Fabiana Bettanin Costa - 2011.pdf: 2024050 bytes, checksum: 3173344e4dab4039f2966cebdd1a98fc (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2011-08-31application/pdfporUniversidade Federal de GoiásPrograma de Pós-graduação em Ciências Farmacêuticas (FF)UFGBrasilFaculdade Farmácia - FF (RG)Embargada pela autora/orientador em 10/04/2013. 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dc.title.eng.fl_str_mv |
Avaliação da atividade antileucêmica in vitro e toxicológica in vivo do composto LQFM-018 |
dc.title.alternative.eng.fl_str_mv |
Evaluation of in vitro anti-leukemic and in vivo toxicologic activity of LQFM-018 lead compound |
title |
Avaliação da atividade antileucêmica in vitro e toxicológica in vivo do composto LQFM-018 |
spellingShingle |
Avaliação da atividade antileucêmica in vitro e toxicológica in vivo do composto LQFM-018 Costa, Fabiana Bettanin K-562 Citotoxicidade Atividade antitumoral Apoptose Necrose Aumento NF-кB K-562 Cytotoxicity Antitumor activity Apoptosis Necrosis Increasing NF-кB CIENCIAS DA SAUDE::FARMACIA |
title_short |
Avaliação da atividade antileucêmica in vitro e toxicológica in vivo do composto LQFM-018 |
title_full |
Avaliação da atividade antileucêmica in vitro e toxicológica in vivo do composto LQFM-018 |
title_fullStr |
Avaliação da atividade antileucêmica in vitro e toxicológica in vivo do composto LQFM-018 |
title_full_unstemmed |
Avaliação da atividade antileucêmica in vitro e toxicológica in vivo do composto LQFM-018 |
title_sort |
Avaliação da atividade antileucêmica in vitro e toxicológica in vivo do composto LQFM-018 |
author |
Costa, Fabiana Bettanin |
author_facet |
Costa, Fabiana Bettanin |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Bozinis, Marize Campos Valadares |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/6157755243167018 |
dc.contributor.referee1.fl_str_mv |
Bozinis, Marize Campos Valadares |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/6157755243167018 |
dc.contributor.referee2.fl_str_mv |
Blanco, Marcos Luengo |
dc.contributor.referee3.fl_str_mv |
Cruz, Andrezza Furquim da |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/2473157789367544 |
dc.contributor.author.fl_str_mv |
Costa, Fabiana Bettanin |
contributor_str_mv |
Bozinis, Marize Campos Valadares Bozinis, Marize Campos Valadares Blanco, Marcos Luengo Cruz, Andrezza Furquim da |
dc.subject.por.fl_str_mv |
K-562 Citotoxicidade Atividade antitumoral Apoptose Necrose Aumento NF-кB |
topic |
K-562 Citotoxicidade Atividade antitumoral Apoptose Necrose Aumento NF-кB K-562 Cytotoxicity Antitumor activity Apoptosis Necrosis Increasing NF-кB CIENCIAS DA SAUDE::FARMACIA |
dc.subject.eng.fl_str_mv |
K-562 Cytotoxicity Antitumor activity Apoptosis Necrosis Increasing NF-кB |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE::FARMACIA |
description |
Cancer is a serious public health problem not only in Brazil but worldwide. Among the various types of cancer known, leukemia is a one of high incidence. In this context, our study aimed to verify the citotoxicity of the compound LQFM-018, in leukemic cells. Both the method of trypan blue exclusion as in the MTT, it was observed a concentration and time dependent response after treatment with the compound LQFM-018. The cell death mechanism was assessed by flow cytometry. The cell cycle analysis showed a decrease of cells in G1 phase with a consequent increase in S phase and G2 / M. The cell death mechanism detected by annexin-V test showed that the K-562 cells were mainly in necrosis. The increased release of LDH also corroborated with the necrotic process. In the treated cells, there was not a significant expression of tumor suppressor protein p-53. The expression of nuclear factor кB increased and decreased expression of ROS. It was also found an increased expression of TNF-R1 receptor, cytochrome-c, decreased ΔΨm and not the expression of proteins Bax and Bcl-2. Acute oral toxicity test was done in vivo. According to the results, the compound LQFM-018 was classified as category 5. The statistical analysis was done using Student t test and ANOVA followed or not by Bonferroni post-test. Was considered statistically significant p<0.05. From these results, we found that the compound LQFM-018 presents potential antitumor activity, but other tests are needed to confirm these results. |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011-08-31 |
dc.date.accessioned.fl_str_mv |
2017-06-07T12:26:50Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
COSTA, F. B. Avaliação da atividade antileucêmica in vitro e toxicológica in vivo do composto LQFM-018. 2011. 110 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2011. |
dc.identifier.uri.fl_str_mv |
http://repositorio.bc.ufg.br/tede/handle/tede/7426 |
identifier_str_mv |
COSTA, F. B. Avaliação da atividade antileucêmica in vitro e toxicológica in vivo do composto LQFM-018. 2011. 110 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2011. |
url |
http://repositorio.bc.ufg.br/tede/handle/tede/7426 |
dc.language.iso.fl_str_mv |
por |
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por |
dc.relation.eng.fl_str_mv |
Embargada pela autora/orientador em 10/04/2013. Autorizado o povoamento pela autora/orientador em 01/06/2017. |
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824936988196152412 |
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600 600 600 |
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6997636413449754996 |
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http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
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http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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Universidade Federal de Goiás |
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UFG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Faculdade Farmácia - FF (RG) |
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Universidade Federal de Goiás |
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