Avaliação da atividade antileucêmica in vitro e toxicológica in vivo do composto LQFM-018

Detalhes bibliográficos
Ano de defesa: 2011
Autor(a) principal: Costa, Fabiana Bettanin lattes
Orientador(a): Bozinis, Marize Campos Valadares lattes
Banca de defesa: Bozinis, Marize Campos Valadares lattes, Blanco, Marcos Luengo, Cruz, Andrezza Furquim da
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de Goiás
Programa de Pós-Graduação: Programa de Pós-graduação em Ciências Farmacêuticas (FF)
Departamento: Faculdade Farmácia - FF (RG)
País: Brasil
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: 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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spelling 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). 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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
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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
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language por
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600
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