Efeito quimiopreventivo e modulador de HLA-G (Human Leukocyte Antigen - G) de Morelloflavona
Autor(a) principal: | |
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Data de Publicação: | 2012 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://hdl.handle.net/11449/124078 http://www.athena.biblioteca.unesp.br/exlibris/bd/cathedra/28-05-2015/000832261.pdf |
Resumo: | The biological and pharmacological activities of biflavonoids are diverse, including their immunosuppressive, anticancer, antioxidant, antiangiogenic, antibacterial, antiviral and antifungal properties. In the present study we assessed the potential ability of morelloflavone, a biflavonoid isolated from Garcinia xanthochymus in modulating the expression of HLA-G (Human Leukocyte Antigen-G), as well as their potential chemopreventive effect. First, we measured the rate of cell death by morelloflavone using Annexin V - Propidium iodide assay in PBMC (peripheral blood mononuclear cells), which showed significant levels of cell death. By flow cytometry was observed the increased expression of HLA-G membrane bound in melanoma cells line (FON) (p < 0.001). Also, was observed the induction of HLA-G soluble in transfected melanoma cells line (M8-HLA-G1) (p < 0.001), with no change to other cell types studied by Enzyme-linked immunosorbent assay - ELISA. The expression of HLA-G mRNA was also induced by morelloflavone, observed by RT-PCR, in melanoma cells (M8) that do not express HLA-G constitutively. Still, we evaluated the chemopreventive activity of morelloflavone. We observed a doubling of quinone reductase enzyme activity in hepatocellular carcinoma cells line (Hepa1c1c7) by quinone reductase assay. By comet assay we were able to verify the genotoxic and antigenotoxic capacity. Regarding antigenotoxicity, morelloflavone caused DNA damage pre treatment. In the posttreatment was observed that morelloflavone may be capable of reversing DNA damage caused by hydrogen peroxide. Thus, the data show that morelloflavone induces the expression of HLA-G and has chemopreventive effect. |
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Efeito quimiopreventivo e modulador de HLA-G (Human Leukocyte Antigen - G) de MorelloflavonaAntigenos de histocompatibilidade HLAQuinonaCancer - QuimioprevençãoAntioxidantesAntioxidantsThe biological and pharmacological activities of biflavonoids are diverse, including their immunosuppressive, anticancer, antioxidant, antiangiogenic, antibacterial, antiviral and antifungal properties. In the present study we assessed the potential ability of morelloflavone, a biflavonoid isolated from Garcinia xanthochymus in modulating the expression of HLA-G (Human Leukocyte Antigen-G), as well as their potential chemopreventive effect. First, we measured the rate of cell death by morelloflavone using Annexin V - Propidium iodide assay in PBMC (peripheral blood mononuclear cells), which showed significant levels of cell death. By flow cytometry was observed the increased expression of HLA-G membrane bound in melanoma cells line (FON) (p < 0.001). Also, was observed the induction of HLA-G soluble in transfected melanoma cells line (M8-HLA-G1) (p < 0.001), with no change to other cell types studied by Enzyme-linked immunosorbent assay - ELISA. The expression of HLA-G mRNA was also induced by morelloflavone, observed by RT-PCR, in melanoma cells (M8) that do not express HLA-G constitutively. Still, we evaluated the chemopreventive activity of morelloflavone. We observed a doubling of quinone reductase enzyme activity in hepatocellular carcinoma cells line (Hepa1c1c7) by quinone reductase assay. By comet assay we were able to verify the genotoxic and antigenotoxic capacity. Regarding antigenotoxicity, morelloflavone caused DNA damage pre treatment. In the posttreatment was observed that morelloflavone may be capable of reversing DNA damage caused by hydrogen peroxide. Thus, the data show that morelloflavone induces the expression of HLA-G and has chemopreventive effect.As atividades biológicas e farmacológicas dos biflavonoides são diversas incluindo suas propriedades imunossupressivas, anticancerígenas, antioxidantes, antiangiogênicas, antibacterianas, antivirais e antifúngicas. No presente estudo, avaliou-se a potencial capacidade do biflavonoide morelloflavona, isolada de Garcinia xanthochymus, em modular a expressão de HLA-G (Human Leukocyte Antigen- G), bem como seu potencial efeito quimiopreventivo. Inicialmente, foi avaliado o índice de morte celular causado pela morelloflavona por meio do ensaio de Anexina V - Iodeto de proídio em PBMC (Células mononucleares do sangue periférico), o qual apresentou índices de morte celular significantes. Através da citometria de fluxo observou-se um aumento da expressão de HLA-G vinculado à membrana celular em linhagens de melanoma (FON) (p < 0,001). Pôde-se observar a indução de HLA-G solúvel em linhagens de melanoma transfectada (M8-HLA-G1) (p < 0,001), sem alteração para os demais tipos celulares estudados, pelo ensaio imunoenzimático- ELISA. A expressão de RNAm de HLA-G também foi induzida pela morelloflavona, observada pela RT- PCR, em células de melanoma M8 que não expressam HLA-G constitutivamente. Ainda, foi avaliada a atividade quimiopreventiva da morelloflavona. Observou-se a duplicação da atividade da enzima quinona redutase na linhagem de hepatocarcinoma celular (Hepa1c1c7) por meio do ensaio quinona redutase. Pelo ensaio do cometa foi possível verificar a capacidade genotóxica e antigenotóxica. Em relação à antigenotoxicidade, a morelloflavona causou dano de DNA no pré-tratamento. No pós-tratamento foi observado que a morelloflavona pode ter a capacidade de reverter danos de DNA causados pelo peróxido de hidrogênio. Sendo assim, os dados demonstrados revelam que a morelloflavona induz a expressão de HLA-G e possui efeito quimiopreventivo.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)FAPESP: 09/52716-4CNPq: 140022/2010-4CAPES: 0103-110Universidade Estadual Paulista (Unesp)Soares, Christiane Pienna [UNESP]Universidade Estadual Paulista (Unesp)Silva, Tarsia Giabardo Alves [UNESP]2015-06-17T19:34:46Z2015-06-17T19:34:46Z2012-11-29info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis187 f : figs, tabsapplication/pdfSILVA, Tarsia Giabardo Alves. Efeito quimiopreventivo e modulador de HLA-G (Human Leukocyte Antigen - G) de Morelloflavona. 2012. 187 f. Tese (doutorado) - Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas, 2012.http://hdl.handle.net/11449/124078000832261http://www.athena.biblioteca.unesp.br/exlibris/bd/cathedra/28-05-2015/000832261.pdf33004030081P717680252903736690000-0003-1740-7360Alephreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPporinfo:eu-repo/semantics/openAccess2024-06-24T18:31:47Zoai:repositorio.unesp.br:11449/124078Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T22:25:38.627239Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Efeito quimiopreventivo e modulador de HLA-G (Human Leukocyte Antigen - G) de Morelloflavona |
title |
Efeito quimiopreventivo e modulador de HLA-G (Human Leukocyte Antigen - G) de Morelloflavona |
spellingShingle |
Efeito quimiopreventivo e modulador de HLA-G (Human Leukocyte Antigen - G) de Morelloflavona Silva, Tarsia Giabardo Alves [UNESP] Antigenos de histocompatibilidade HLA Quinona Cancer - Quimioprevenção Antioxidantes Antioxidants |
title_short |
Efeito quimiopreventivo e modulador de HLA-G (Human Leukocyte Antigen - G) de Morelloflavona |
title_full |
Efeito quimiopreventivo e modulador de HLA-G (Human Leukocyte Antigen - G) de Morelloflavona |
title_fullStr |
Efeito quimiopreventivo e modulador de HLA-G (Human Leukocyte Antigen - G) de Morelloflavona |
title_full_unstemmed |
Efeito quimiopreventivo e modulador de HLA-G (Human Leukocyte Antigen - G) de Morelloflavona |
title_sort |
Efeito quimiopreventivo e modulador de HLA-G (Human Leukocyte Antigen - G) de Morelloflavona |
author |
Silva, Tarsia Giabardo Alves [UNESP] |
author_facet |
Silva, Tarsia Giabardo Alves [UNESP] |
author_role |
author |
dc.contributor.none.fl_str_mv |
Soares, Christiane Pienna [UNESP] Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Silva, Tarsia Giabardo Alves [UNESP] |
dc.subject.por.fl_str_mv |
Antigenos de histocompatibilidade HLA Quinona Cancer - Quimioprevenção Antioxidantes Antioxidants |
topic |
Antigenos de histocompatibilidade HLA Quinona Cancer - Quimioprevenção Antioxidantes Antioxidants |
description |
The biological and pharmacological activities of biflavonoids are diverse, including their immunosuppressive, anticancer, antioxidant, antiangiogenic, antibacterial, antiviral and antifungal properties. In the present study we assessed the potential ability of morelloflavone, a biflavonoid isolated from Garcinia xanthochymus in modulating the expression of HLA-G (Human Leukocyte Antigen-G), as well as their potential chemopreventive effect. First, we measured the rate of cell death by morelloflavone using Annexin V - Propidium iodide assay in PBMC (peripheral blood mononuclear cells), which showed significant levels of cell death. By flow cytometry was observed the increased expression of HLA-G membrane bound in melanoma cells line (FON) (p < 0.001). Also, was observed the induction of HLA-G soluble in transfected melanoma cells line (M8-HLA-G1) (p < 0.001), with no change to other cell types studied by Enzyme-linked immunosorbent assay - ELISA. The expression of HLA-G mRNA was also induced by morelloflavone, observed by RT-PCR, in melanoma cells (M8) that do not express HLA-G constitutively. Still, we evaluated the chemopreventive activity of morelloflavone. We observed a doubling of quinone reductase enzyme activity in hepatocellular carcinoma cells line (Hepa1c1c7) by quinone reductase assay. By comet assay we were able to verify the genotoxic and antigenotoxic capacity. Regarding antigenotoxicity, morelloflavone caused DNA damage pre treatment. In the posttreatment was observed that morelloflavone may be capable of reversing DNA damage caused by hydrogen peroxide. Thus, the data show that morelloflavone induces the expression of HLA-G and has chemopreventive effect. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-11-29 2015-06-17T19:34:46Z 2015-06-17T19:34:46Z |
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 |
SILVA, Tarsia Giabardo Alves. Efeito quimiopreventivo e modulador de HLA-G (Human Leukocyte Antigen - G) de Morelloflavona. 2012. 187 f. Tese (doutorado) - Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas, 2012. http://hdl.handle.net/11449/124078 000832261 http://www.athena.biblioteca.unesp.br/exlibris/bd/cathedra/28-05-2015/000832261.pdf 33004030081P7 1768025290373669 0000-0003-1740-7360 |
identifier_str_mv |
SILVA, Tarsia Giabardo Alves. Efeito quimiopreventivo e modulador de HLA-G (Human Leukocyte Antigen - G) de Morelloflavona. 2012. 187 f. Tese (doutorado) - Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas, 2012. 000832261 33004030081P7 1768025290373669 0000-0003-1740-7360 |
url |
http://hdl.handle.net/11449/124078 http://www.athena.biblioteca.unesp.br/exlibris/bd/cathedra/28-05-2015/000832261.pdf |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
187 f : figs, tabs 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) |
instacron_str |
UNESP |
institution |
UNESP |
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 |
|
_version_ |
1808129426878103552 |