Estudo das propriedades anticÃncer In Vitro e In Vivo do 15-Deoxigoiazensolido
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2008 |
| Tipo de documento: | Tese |
| Idioma: | por |
| Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFC |
| Texto Completo: | http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=3150 |
Resumo: | The present study evaluated the anticancer activity of sesquiterpene lactone 15-deoxygoyazensolido. Citotoxic activity was initially evaluated by the MTT assay, where 15-deoxygoyazensolido showed IC50 < 4 μg/mL in all tested cell lines, varying from 0,09 to 0,56 μg/mL. This activity was confirmed by Trypan Blue assay, which 15-deoxygoyazensolido showed activity at 0,25, 0,5 and 1 μg/mL after 24h exposition in HL-60 cells. Afterwards, it was reveled by incorporation test of BrdU that citotoxic activity of 15-deoxygoyazensolido is related to inhibition of DNA synthesis. Besides, on the assays for induction of cellular apoptosis showed morphological alterations, DNA fragmentation, mitochondria depolarization, maintaining membrane integrity, typical apoptosis sight. The in vivo activity of 15-deoxygoyazensolido was evaluated using sarmoca 180 tumor in mice and Walker 256 tumor in rats. The sesquiterpene lactone inhibited tumor growth in a dose-dependent manner, but it was not capable to increase mice survival. The administration of 15-deoxygoyazensolido at dose 10 mg/m2/day inhibited 49,39% of solid Sarcoma 180 tumor development in transplanted mice. The histophatological assay in mice organs reveled moderate liver toxicity but these effects are considered reversible. The administration of sesquiterpene lactone inhibited Walker 256 tumor development at doses 5 e 10 mg/kg/day in transplanted rats about 34,05 e 38,80 % respectively. Concerning allergenic properties, it was not detected anti-lactone IgE antibody synthesis in swiss mice immunized with 100 μg of 15-deoxygoyazensolido. The results show that 15-deoxigoiazensolido has a potent anticancer activity, being apoptosis the mechanism of action which takes tumor cells to death. |
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info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisEstudo das propriedades anticÃncer In Vitro e In Vivo do 15-DeoxigoiazensolidoEVALUATION OF IN VITRO AND IN VIVO ANTICANCER ACTIVITY OF 15-DEOXYGOYAZENSOLIDE.2008-08-22LetÃcia Veras Costa-Lotufo43089810344http://lattes.cnpq.br/5193149437979818Manoel Odorico de Moraes Filho04854543353http://lattes.cnpq.br/0701679734111287Ana Paula Negreiros Nunes Alves19242662372http://lattes.cnpq.br/5522921433940881 Norberto Peporine Lopes09903491875http://buscatextual.cnpq.br/buscatextual/visualizacv.jsp?id=K4793478Z3Maria Izabel Florindo Guedes47501723753http://lattes.cnpq.br/528277114330603462961993334http://buscatextual.cnpq.br/buscatextual/visualizacv.jsp?id=K4769112A4MÃrcio Roberto Pinho PereiraUniversidade Federal do CearÃPrograma de PÃs-GraduaÃÃo em FarmacologiaUFCBRNeoplasia Apoptosis LactoneFARMACOLOGIA GERALThe present study evaluated the anticancer activity of sesquiterpene lactone 15-deoxygoyazensolido. Citotoxic activity was initially evaluated by the MTT assay, where 15-deoxygoyazensolido showed IC50 < 4 μg/mL in all tested cell lines, varying from 0,09 to 0,56 μg/mL. This activity was confirmed by Trypan Blue assay, which 15-deoxygoyazensolido showed activity at 0,25, 0,5 and 1 μg/mL after 24h exposition in HL-60 cells. Afterwards, it was reveled by incorporation test of BrdU that citotoxic activity of 15-deoxygoyazensolido is related to inhibition of DNA synthesis. Besides, on the assays for induction of cellular apoptosis showed morphological alterations, DNA fragmentation, mitochondria depolarization, maintaining membrane integrity, typical apoptosis sight. The in vivo activity of 15-deoxygoyazensolido was evaluated using sarmoca 180 tumor in mice and Walker 256 tumor in rats. The sesquiterpene lactone inhibited tumor growth in a dose-dependent manner, but it was not capable to increase mice survival. The administration of 15-deoxygoyazensolido at dose 10 mg/m2/day inhibited 49,39% of solid Sarcoma 180 tumor development in transplanted mice. The histophatological assay in mice organs reveled moderate liver toxicity but these effects are considered reversible. The administration of sesquiterpene lactone inhibited Walker 256 tumor development at doses 5 e 10 mg/kg/day in transplanted rats about 34,05 e 38,80 % respectively. Concerning allergenic properties, it was not detected anti-lactone IgE antibody synthesis in swiss mice immunized with 100 μg of 15-deoxygoyazensolido. The results show that 15-deoxigoiazensolido has a potent anticancer activity, being apoptosis the mechanism of action which takes tumor cells to death.O presente estudo procurou avaliar a atividade anticÃncer da lactona sesquiterpÃnica 15-deoxigoiazensolido. A atividade citotÃxica foi inicialmente avaliada pelo mÃtodo do MTT, onde o 15-deoxigoiazensolido obteve uma IC50 < 4 μg/mL em todas as linhagens testadas variando de 0,09 a 0,56 μg/mL. Essa atividade foi confirmada pelo mÃtodo do Azul de Tripan, no qual o 15-deoxigoiazensolido mostrou atividade nas doses de 0,25, 0,5 e 1 μg/mL apÃs exposiÃÃo por 24 h na linhagem HL-60. Em seguida, foi revelado pelo teste de incorporaÃÃo do Brdu que a atividade citotÃxica do 15-deoxigoiazensolido està relacionada com a inibiÃÃo da sÃntese de DNA. AlÃm disso, os ensaios que avaliam a induÃÃo de morte celular mostraram alteraÃÃes morfolÃgicas, fragmentaÃÃo do DNA, despolarizaÃÃo da mitocÃndria e manutenÃÃo da integridade da membrana celular, caracterÃsticas do processo de apoptose. A atividade in vivo do 15-deoxigoiazensolido foi avaliado utilizando-se o sarcoma 180 em camundongos e Walker 256 em ratos. A lactona sesquiterpÃnica inibiu o crescimento do volume tumoral do sarcoma 180 de maneira dose dependente, mas nÃo foi capaz de aumentar a sobrevida dos animais. A administraÃÃo do 15-deoxigoiazensolido na dose de 10 mg/m2/dia inibiu 49,39 % do desenvolvimento do tumor sÃlido em camundongos transplantados com Sarcoma 180. A anÃlise histopatolÃgica nos ÃrgÃos dos camundongos revelou que houve moderada toxicidade no fÃgado, mas os efeitos sÃo passiveis de reversibilidade. A administraÃÃo da lactona sesquiterpÃnica nas doses de 5 e 10 mg/kg/dia em ratos transplantados com o tumor de Walker 256 inibiu seu desenvolvimento em cerca de 34,05 e 38,80 % respectivamente. Em relaÃÃo ao seu potencial alergÃnico, nÃo foi detectado sÃntese de anticorpos IgE anti-lactona em camundongos Swiss. Os resultados mostram que o 15-deoxigoiazensolido tem potente atividade anticÃncer, sendo a apoptose o mecanismo de aÃÃo que leva as cÃlulas tumorais à morte.nÃo hÃhttp://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=3150application/pdfinfo:eu-repo/semantics/openAccessporreponame:Biblioteca Digital de Teses e Dissertações da UFCinstname:Universidade Federal do Cearáinstacron:UFC2019-01-21T11:16:21Zmail@mail.com - |
| dc.title.pt.fl_str_mv |
Estudo das propriedades anticÃncer In Vitro e In Vivo do 15-Deoxigoiazensolido |
| dc.title.alternative..fl_str_mv |
EVALUATION OF IN VITRO AND IN VIVO ANTICANCER ACTIVITY OF 15-DEOXYGOYAZENSOLIDE. |
| title |
Estudo das propriedades anticÃncer In Vitro e In Vivo do 15-Deoxigoiazensolido |
| spellingShingle |
Estudo das propriedades anticÃncer In Vitro e In Vivo do 15-Deoxigoiazensolido MÃrcio Roberto Pinho Pereira FARMACOLOGIA GERAL |
| title_short |
Estudo das propriedades anticÃncer In Vitro e In Vivo do 15-Deoxigoiazensolido |
| title_full |
Estudo das propriedades anticÃncer In Vitro e In Vivo do 15-Deoxigoiazensolido |
| title_fullStr |
Estudo das propriedades anticÃncer In Vitro e In Vivo do 15-Deoxigoiazensolido |
| title_full_unstemmed |
Estudo das propriedades anticÃncer In Vitro e In Vivo do 15-Deoxigoiazensolido |
| title_sort |
Estudo das propriedades anticÃncer In Vitro e In Vivo do 15-Deoxigoiazensolido |
| author |
MÃrcio Roberto Pinho Pereira |
| author_facet |
MÃrcio Roberto Pinho Pereira |
| author_role |
author |
| dc.contributor.advisor1.fl_str_mv |
LetÃcia Veras Costa-Lotufo |
| dc.contributor.advisor1ID.fl_str_mv |
43089810344 |
| dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/5193149437979818 |
| dc.contributor.referee1.fl_str_mv |
Manoel Odorico de Moraes Filho |
| dc.contributor.referee1ID.fl_str_mv |
04854543353 |
| dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/0701679734111287 |
| dc.contributor.referee2.fl_str_mv |
Ana Paula Negreiros Nunes Alves |
| dc.contributor.referee2ID.fl_str_mv |
19242662372 |
| dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/5522921433940881 |
| dc.contributor.referee3.fl_str_mv |
Norberto Peporine Lopes |
| dc.contributor.referee3ID.fl_str_mv |
09903491875 |
| dc.contributor.referee3Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.jsp?id=K4793478Z3 |
| dc.contributor.referee4.fl_str_mv |
Maria Izabel Florindo Guedes |
| dc.contributor.referee4ID.fl_str_mv |
47501723753 |
| dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/5282771143306034 |
| dc.contributor.authorID.fl_str_mv |
62961993334 |
| dc.contributor.authorLattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.jsp?id=K4769112A4 |
| dc.contributor.author.fl_str_mv |
MÃrcio Roberto Pinho Pereira |
| contributor_str_mv |
LetÃcia Veras Costa-Lotufo Manoel Odorico de Moraes Filho Ana Paula Negreiros Nunes Alves Norberto Peporine Lopes Maria Izabel Florindo Guedes |
| dc.subject.cnpq.fl_str_mv |
FARMACOLOGIA GERAL |
| topic |
FARMACOLOGIA GERAL |
| dc.description.sponsorship.fl_txt_mv |
nÃo hà |
| dc.description.abstract..fl_txt_mv |
The present study evaluated the anticancer activity of sesquiterpene lactone 15-deoxygoyazensolido. Citotoxic activity was initially evaluated by the MTT assay, where 15-deoxygoyazensolido showed IC50 < 4 μg/mL in all tested cell lines, varying from 0,09 to 0,56 μg/mL. This activity was confirmed by Trypan Blue assay, which 15-deoxygoyazensolido showed activity at 0,25, 0,5 and 1 μg/mL after 24h exposition in HL-60 cells. Afterwards, it was reveled by incorporation test of BrdU that citotoxic activity of 15-deoxygoyazensolido is related to inhibition of DNA synthesis. Besides, on the assays for induction of cellular apoptosis showed morphological alterations, DNA fragmentation, mitochondria depolarization, maintaining membrane integrity, typical apoptosis sight. The in vivo activity of 15-deoxygoyazensolido was evaluated using sarmoca 180 tumor in mice and Walker 256 tumor in rats. The sesquiterpene lactone inhibited tumor growth in a dose-dependent manner, but it was not capable to increase mice survival. The administration of 15-deoxygoyazensolido at dose 10 mg/m2/day inhibited 49,39% of solid Sarcoma 180 tumor development in transplanted mice. The histophatological assay in mice organs reveled moderate liver toxicity but these effects are considered reversible. The administration of sesquiterpene lactone inhibited Walker 256 tumor development at doses 5 e 10 mg/kg/day in transplanted rats about 34,05 e 38,80 % respectively. Concerning allergenic properties, it was not detected anti-lactone IgE antibody synthesis in swiss mice immunized with 100 μg of 15-deoxygoyazensolido. The results show that 15-deoxigoiazensolido has a potent anticancer activity, being apoptosis the mechanism of action which takes tumor cells to death. |
| dc.description.abstract.por.fl_txt_mv |
O presente estudo procurou avaliar a atividade anticÃncer da lactona sesquiterpÃnica 15-deoxigoiazensolido. A atividade citotÃxica foi inicialmente avaliada pelo mÃtodo do MTT, onde o 15-deoxigoiazensolido obteve uma IC50 < 4 μg/mL em todas as linhagens testadas variando de 0,09 a 0,56 μg/mL. Essa atividade foi confirmada pelo mÃtodo do Azul de Tripan, no qual o 15-deoxigoiazensolido mostrou atividade nas doses de 0,25, 0,5 e 1 μg/mL apÃs exposiÃÃo por 24 h na linhagem HL-60. Em seguida, foi revelado pelo teste de incorporaÃÃo do Brdu que a atividade citotÃxica do 15-deoxigoiazensolido està relacionada com a inibiÃÃo da sÃntese de DNA. AlÃm disso, os ensaios que avaliam a induÃÃo de morte celular mostraram alteraÃÃes morfolÃgicas, fragmentaÃÃo do DNA, despolarizaÃÃo da mitocÃndria e manutenÃÃo da integridade da membrana celular, caracterÃsticas do processo de apoptose. A atividade in vivo do 15-deoxigoiazensolido foi avaliado utilizando-se o sarcoma 180 em camundongos e Walker 256 em ratos. A lactona sesquiterpÃnica inibiu o crescimento do volume tumoral do sarcoma 180 de maneira dose dependente, mas nÃo foi capaz de aumentar a sobrevida dos animais. A administraÃÃo do 15-deoxigoiazensolido na dose de 10 mg/m2/dia inibiu 49,39 % do desenvolvimento do tumor sÃlido em camundongos transplantados com Sarcoma 180. A anÃlise histopatolÃgica nos ÃrgÃos dos camundongos revelou que houve moderada toxicidade no fÃgado, mas os efeitos sÃo passiveis de reversibilidade. A administraÃÃo da lactona sesquiterpÃnica nas doses de 5 e 10 mg/kg/dia em ratos transplantados com o tumor de Walker 256 inibiu seu desenvolvimento em cerca de 34,05 e 38,80 % respectivamente. Em relaÃÃo ao seu potencial alergÃnico, nÃo foi detectado sÃntese de anticorpos IgE anti-lactona em camundongos Swiss. Os resultados mostram que o 15-deoxigoiazensolido tem potente atividade anticÃncer, sendo a apoptose o mecanismo de aÃÃo que leva as cÃlulas tumorais à morte. |
| description |
The present study evaluated the anticancer activity of sesquiterpene lactone 15-deoxygoyazensolido. Citotoxic activity was initially evaluated by the MTT assay, where 15-deoxygoyazensolido showed IC50 < 4 μg/mL in all tested cell lines, varying from 0,09 to 0,56 μg/mL. This activity was confirmed by Trypan Blue assay, which 15-deoxygoyazensolido showed activity at 0,25, 0,5 and 1 μg/mL after 24h exposition in HL-60 cells. Afterwards, it was reveled by incorporation test of BrdU that citotoxic activity of 15-deoxygoyazensolido is related to inhibition of DNA synthesis. Besides, on the assays for induction of cellular apoptosis showed morphological alterations, DNA fragmentation, mitochondria depolarization, maintaining membrane integrity, typical apoptosis sight. The in vivo activity of 15-deoxygoyazensolido was evaluated using sarmoca 180 tumor in mice and Walker 256 tumor in rats. The sesquiterpene lactone inhibited tumor growth in a dose-dependent manner, but it was not capable to increase mice survival. The administration of 15-deoxygoyazensolido at dose 10 mg/m2/day inhibited 49,39% of solid Sarcoma 180 tumor development in transplanted mice. The histophatological assay in mice organs reveled moderate liver toxicity but these effects are considered reversible. The administration of sesquiterpene lactone inhibited Walker 256 tumor development at doses 5 e 10 mg/kg/day in transplanted rats about 34,05 e 38,80 % respectively. Concerning allergenic properties, it was not detected anti-lactone IgE antibody synthesis in swiss mice immunized with 100 μg of 15-deoxygoyazensolido. The results show that 15-deoxigoiazensolido has a potent anticancer activity, being apoptosis the mechanism of action which takes tumor cells to death. |
| publishDate |
2008 |
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2008-08-22 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/doctoralThesis |
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publishedVersion |
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doctoralThesis |
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http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=3150 |
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http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=3150 |
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por |
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por |
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openAccess |
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Universidade Federal do Cearà |
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Programa de PÃs-GraduaÃÃo em Farmacologia |
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UFC |
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BR |
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Universidade Federal do Cearà |
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reponame:Biblioteca Digital de Teses e Dissertações da UFC instname:Universidade Federal do Ceará instacron:UFC |
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