Efeitos toxicogenéticos e toxicogenômicos do Isotiocianato de Alila (óleo de mostarda) em linhagens celulares de carcinoma de bexiga

Detalhes bibliográficos
Autor(a) principal: Sávio, André Luiz Ventura [UNESP]
Data de Publicação: 2014
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://hdl.handle.net/11449/113891
Resumo: Compounds obtained from fruits, vegetables and essential oils have been widely used to treat many diseases. The allyl isothiocyanate (AITC), also known as mustard essential oil, is found in plants of the cruciferous family and is abundant in the mustard seeds. Due to its high bioavailability in urine, AITC has been considered as a promising antineoplastic agent against bladder cancer. Therefore, the aims of this study were to investigate the toxicogenetic and toxicogenomic effects of AITC in the wild-type (RT4) and in a mutant (T24) TP53 bladder transitional carcinoma cell lines. AITC was tested at concentrations of 0.005, 0.0625, 0.0725, 0.0825, 0.0925, 0.125 and 0.25 μM in the cytotoxicity and cell and clonogenic survival assays; in the comet and micronucleus assays, flow cytometry, apoptosis and gene expression (ANLN, BAX, BCL-2, CDK-1, SMAD4, S100P e TP53) evaluations the concentrations of 0.005; 0.0625; 0.0725; 0.0825 e 0.0925 μM were used. The results showed increased primary DNA damage in T24 (0.005, 0.0625, 0.0725, 0.0825 and 0.0925 μM) and RT4 (0.0725, 0.0825 and 0.0925 μM) cells. However, no significant difference was detected in the frequency of micronucleated cells. A significant increase of cells at sub-G1 phase (0.0625, 0.0725 and 0.0825 μM) and significant decrease at S phase (0.005, 0.0625, 0.0725 and 0.0825 μM) were observed in RT4 cells after AITC treatments. In T24 cells, an increased sub-G1 rate (0.0725 and 0.0825 μM) and cell cycle arrest at G2 phase (0.0625, 0.0725 and 0.0825 μM) were detected. Furthermore, it was observed increased apoptosis and necrosis rates and increase of S100P and BAX and decrease of BCL-2 expression in the wild type TP53 cells. For the mutated TP53 cell line, increased expression of BCL-2, BAX and ANLN and decreased expression S100P were observed. No change was detected for the SMAD4 and CDK-1 genes. In conclusion, AITC was able to reach DNA and induce primary damage in both bladder ...
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spelling Efeitos toxicogenéticos e toxicogenômicos do Isotiocianato de Alila (óleo de mostarda) em linhagens celulares de carcinoma de bexigaBexiga - CâncerExpressão gênicaIsotiocianatosCruciferaToxicologia genéticaPlantas - ToxinasÓleos vegetaisPlant toxinsCompounds obtained from fruits, vegetables and essential oils have been widely used to treat many diseases. The allyl isothiocyanate (AITC), also known as mustard essential oil, is found in plants of the cruciferous family and is abundant in the mustard seeds. Due to its high bioavailability in urine, AITC has been considered as a promising antineoplastic agent against bladder cancer. Therefore, the aims of this study were to investigate the toxicogenetic and toxicogenomic effects of AITC in the wild-type (RT4) and in a mutant (T24) TP53 bladder transitional carcinoma cell lines. AITC was tested at concentrations of 0.005, 0.0625, 0.0725, 0.0825, 0.0925, 0.125 and 0.25 μM in the cytotoxicity and cell and clonogenic survival assays; in the comet and micronucleus assays, flow cytometry, apoptosis and gene expression (ANLN, BAX, BCL-2, CDK-1, SMAD4, S100P e TP53) evaluations the concentrations of 0.005; 0.0625; 0.0725; 0.0825 e 0.0925 μM were used. The results showed increased primary DNA damage in T24 (0.005, 0.0625, 0.0725, 0.0825 and 0.0925 μM) and RT4 (0.0725, 0.0825 and 0.0925 μM) cells. However, no significant difference was detected in the frequency of micronucleated cells. A significant increase of cells at sub-G1 phase (0.0625, 0.0725 and 0.0825 μM) and significant decrease at S phase (0.005, 0.0625, 0.0725 and 0.0825 μM) were observed in RT4 cells after AITC treatments. In T24 cells, an increased sub-G1 rate (0.0725 and 0.0825 μM) and cell cycle arrest at G2 phase (0.0625, 0.0725 and 0.0825 μM) were detected. Furthermore, it was observed increased apoptosis and necrosis rates and increase of S100P and BAX and decrease of BCL-2 expression in the wild type TP53 cells. For the mutated TP53 cell line, increased expression of BCL-2, BAX and ANLN and decreased expression S100P were observed. No change was detected for the SMAD4 and CDK-1 genes. In conclusion, AITC was able to reach DNA and induce primary damage in both bladder ...Nos últimos anos, tem crescido o interesse pela identificação de compostos naturais com potencial medicinal. O isotiocianato de alila (AITC), encontrado em plantas da família Cruciferae e composto majoritário da semente de mostarda, vem sendo avaliado quanto a sua atividade antineoplásica em bexiga devido à sua alta biodisponibilidade na urina a após ingestão. Neste estudo foram investigadas as atividades toxicogenética e toxicogenômica do AITC em linhagens celulares de carcinoma de bexiga com diferentes status do gene TP53 (RT4 – TP53 selvagem / T24 – TP53 mutado). As concentrações de AITC testadas nos ensaios de citotoxicidade, sobrevivência celular e clonogênica foram 0,005, 0,0625, 0,0725, 0,0825, 0,0925, 0,125 e 0,25 μM; nos testes do cometa, micronúcleo, ciclo celular, apoptose, morfologia e expressão gênica (ANLN, BAX, BCL-2, CDK-1, SMAD4, S100P e TP53) foram utilizadas as concentrações de 0,005, 0,0625, 0,0725, 0,0825 e 0,0925 μM. Os resultados mostraram aumento de danos primários no DNA (teste do cometa) para todas as concentrações testadas do AITC na linhagem T24 e para as concentrações mais altas (0,0725, 0,0825 e 0,0925 μM) na linhagem RT4; não foram observados aumentos nas frequências de células micronucleadas em ambas as linhagens. Nas análises de ciclo celular e apoptose foram observadas a parada do ciclo na fase G2/M para a linhagem T24 e altas taxas de apoptose precoce e necrose na linhagem RT4. Com relação à expressão gênica, houve aumento da expressão de S100P e BAX e diminuição da expressão de BCL-2 na linhagem RT4 e aumento da expressão de BCL-2, BAX e ANLN e diminuição da expressão de S100P na T24. Nenhuma alteração foi identificada para os genes SMAD4 e CDK1 nas duas linhagens tratadas com o AITC. Concluindo, o AITC foi capaz de induzir lesões primárias no DNA de células de ambas as linhagens de carcinoma de bexiga, mas que não se refletiram ...Universidade Estadual Paulista (Unesp)Salvadori, Daisy Maria Favero [UNESP]Silva, Glenda Nicioli da [UNESP]Universidade Estadual Paulista (Unesp)Sávio, André Luiz Ventura [UNESP]2015-01-26T13:21:21Z2015-01-26T13:21:21Z2014-07-25info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis93 f.application/pdfSÁVIO, André Luiz Ventura. Efeitos toxicogenéticos e toxicogenômicos do Isotiocianato de Alila (óleo de mostarda) em linhagens celulares de carcinoma de bexiga. 2014. 93 f. Dissertação (mestrado) - Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Medicina de Botucatu, 2014.http://hdl.handle.net/11449/113891000795967000795967.pdf33004064056P55051118752980903Alephreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPporinfo:eu-repo/semantics/openAccess2024-09-03T19:04:00Zoai:repositorio.unesp.br:11449/113891Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-09-03T19:04Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Efeitos toxicogenéticos e toxicogenômicos do Isotiocianato de Alila (óleo de mostarda) em linhagens celulares de carcinoma de bexiga
title Efeitos toxicogenéticos e toxicogenômicos do Isotiocianato de Alila (óleo de mostarda) em linhagens celulares de carcinoma de bexiga
spellingShingle Efeitos toxicogenéticos e toxicogenômicos do Isotiocianato de Alila (óleo de mostarda) em linhagens celulares de carcinoma de bexiga
Sávio, André Luiz Ventura [UNESP]
Bexiga - Câncer
Expressão gênica
Isotiocianatos
Crucifera
Toxicologia genética
Plantas - Toxinas
Óleos vegetais
Plant toxins
title_short Efeitos toxicogenéticos e toxicogenômicos do Isotiocianato de Alila (óleo de mostarda) em linhagens celulares de carcinoma de bexiga
title_full Efeitos toxicogenéticos e toxicogenômicos do Isotiocianato de Alila (óleo de mostarda) em linhagens celulares de carcinoma de bexiga
title_fullStr Efeitos toxicogenéticos e toxicogenômicos do Isotiocianato de Alila (óleo de mostarda) em linhagens celulares de carcinoma de bexiga
title_full_unstemmed Efeitos toxicogenéticos e toxicogenômicos do Isotiocianato de Alila (óleo de mostarda) em linhagens celulares de carcinoma de bexiga
title_sort Efeitos toxicogenéticos e toxicogenômicos do Isotiocianato de Alila (óleo de mostarda) em linhagens celulares de carcinoma de bexiga
author Sávio, André Luiz Ventura [UNESP]
author_facet Sávio, André Luiz Ventura [UNESP]
author_role author
dc.contributor.none.fl_str_mv Salvadori, Daisy Maria Favero [UNESP]
Silva, Glenda Nicioli da [UNESP]
Universidade Estadual Paulista (Unesp)
dc.contributor.author.fl_str_mv Sávio, André Luiz Ventura [UNESP]
dc.subject.por.fl_str_mv Bexiga - Câncer
Expressão gênica
Isotiocianatos
Crucifera
Toxicologia genética
Plantas - Toxinas
Óleos vegetais
Plant toxins
topic Bexiga - Câncer
Expressão gênica
Isotiocianatos
Crucifera
Toxicologia genética
Plantas - Toxinas
Óleos vegetais
Plant toxins
description Compounds obtained from fruits, vegetables and essential oils have been widely used to treat many diseases. The allyl isothiocyanate (AITC), also known as mustard essential oil, is found in plants of the cruciferous family and is abundant in the mustard seeds. Due to its high bioavailability in urine, AITC has been considered as a promising antineoplastic agent against bladder cancer. Therefore, the aims of this study were to investigate the toxicogenetic and toxicogenomic effects of AITC in the wild-type (RT4) and in a mutant (T24) TP53 bladder transitional carcinoma cell lines. AITC was tested at concentrations of 0.005, 0.0625, 0.0725, 0.0825, 0.0925, 0.125 and 0.25 μM in the cytotoxicity and cell and clonogenic survival assays; in the comet and micronucleus assays, flow cytometry, apoptosis and gene expression (ANLN, BAX, BCL-2, CDK-1, SMAD4, S100P e TP53) evaluations the concentrations of 0.005; 0.0625; 0.0725; 0.0825 e 0.0925 μM were used. The results showed increased primary DNA damage in T24 (0.005, 0.0625, 0.0725, 0.0825 and 0.0925 μM) and RT4 (0.0725, 0.0825 and 0.0925 μM) cells. However, no significant difference was detected in the frequency of micronucleated cells. A significant increase of cells at sub-G1 phase (0.0625, 0.0725 and 0.0825 μM) and significant decrease at S phase (0.005, 0.0625, 0.0725 and 0.0825 μM) were observed in RT4 cells after AITC treatments. In T24 cells, an increased sub-G1 rate (0.0725 and 0.0825 μM) and cell cycle arrest at G2 phase (0.0625, 0.0725 and 0.0825 μM) were detected. Furthermore, it was observed increased apoptosis and necrosis rates and increase of S100P and BAX and decrease of BCL-2 expression in the wild type TP53 cells. For the mutated TP53 cell line, increased expression of BCL-2, BAX and ANLN and decreased expression S100P were observed. No change was detected for the SMAD4 and CDK-1 genes. In conclusion, AITC was able to reach DNA and induce primary damage in both bladder ...
publishDate 2014
dc.date.none.fl_str_mv 2014-07-25
2015-01-26T13:21:21Z
2015-01-26T13:21:21Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv SÁVIO, André Luiz Ventura. Efeitos toxicogenéticos e toxicogenômicos do Isotiocianato de Alila (óleo de mostarda) em linhagens celulares de carcinoma de bexiga. 2014. 93 f. Dissertação (mestrado) - Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Medicina de Botucatu, 2014.
http://hdl.handle.net/11449/113891
000795967
000795967.pdf
33004064056P5
5051118752980903
identifier_str_mv SÁVIO, André Luiz Ventura. Efeitos toxicogenéticos e toxicogenômicos do Isotiocianato de Alila (óleo de mostarda) em linhagens celulares de carcinoma de bexiga. 2014. 93 f. Dissertação (mestrado) - Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Medicina de Botucatu, 2014.
000795967
000795967.pdf
33004064056P5
5051118752980903
url http://hdl.handle.net/11449/113891
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.format.none.fl_str_mv 93 f.
application/pdf
dc.publisher.none.fl_str_mv Universidade Estadual Paulista (Unesp)
publisher.none.fl_str_mv Universidade Estadual Paulista (Unesp)
dc.source.none.fl_str_mv Aleph
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
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reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv repositoriounesp@unesp.br
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