Avalia??o do potencial antitumoral de flavon?ides polihidroxilados sobre c?lulas de glioblastoma humano
Ano de defesa: | 2011 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Estadual de Feira de Santana
|
Programa de Pós-Graduação: |
Doutorado Acad?mico em Biotecnologia
|
Departamento: |
DEPARTAMENTO DE CI?NCIAS BIOL?GICAS
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://tede2.uefs.br:8080/handle/tede/1069 |
Resumo: | In this work, we investigated the effect of polyhydroxilic flavonoids 5,7-dihydroxiflavone (crisin), 3?,4?-dihydroxyflavone, 4?,5,7-trihidroxiflavone (apigenin), 3,4',5,7-tetrahidroxiflavone (kaempferol), 3,3?,4?,5,6-pentahydroxyflavone (quercetin), and 3,3?,4?,5,7-pentahydroxyflavone-3-rutinoside (rutin) on cell viability, phenotypic change, in migratory and invasive capacity in cultured of human glioblastoma multiform cells, using as a model the highly proliferative human cell line GL-15. In a first study we investigated the effects of the flavonoid rutin (3,3',4',5,7-pentahydroxyflavone-3-rutinoside) on growth, viability and morphology of glioblastoma cells. We observed that rutin (50-100 ?M) reduced proliferation and viability of GL-15 cells, leading to decreased levels of ERK1/2 phosphorylation (P-ERK1/2) and accumulation of cells in the G2 phase of the cell cycle. On the other hand, 87.4% of GL-15 cells exposed to 100 ?M rutin entered apoptosis, as revealed by flow cytometry after AnnexinV/PI staining. Nuclear condensation and DNA fragmentation were also observed, further confirming that apoptosis had occurred. Moreover, the remaining cells that were treated with 50 ?M rutin presented a morphological pattern of astroglial differentiation in culture, characterised by a condensed cell body and thin processes with over expression of GFAP. In second study, we investigated the effects of rutin and the others polyhydroxylated flavonoids on viability, morphology, and structure of GL-15 gliobastoma cells, and also the effects on regulation of elements involved in cellular invasion, as cell migration, and expression of MEC, MMPs, and CX43. We observed that, measuring mitochondrial metabolism through MTT-teste, that flavonoids chrysin, apigenin and 3',4'-dihydroxyflavone induced a significative reduction in viability GL-15 cells, besides ultrastructural features of apoptosis. Flavonoids tested also induced morphological changes in GL-15 cells, which acquired a phenotype pattern of astrocytic differentiation, characterized by the presence of a condensed cell body and thin and long cellular processes, expressing GFAP. Scanning electron microscopy showed that flavonoids induced a reduction in filopodia-like structures on the cell surface of GL-15 cells. We found that flavonoids induced a delay in the migration capacity of glioblastoma cells, after the first 12 h after treatment, and cells exhibited increase in intra and extracellular expression fibronectin, and mainly intracellular expression of laminin. Moreover, we also observed that flavonoids induced reduction on MMP-2 expression and MMP activity, and a reduction on Cx43 expression after treatment with rutin. Taken together, these finds show that rutin and polyhydroxylated flavonoids can inhibit the growth, induce morphological changes or apoptosis, and regulate the expression of components involved in tumor cell migration and invasion, these molecules may be considered as potential adjuvants for therapy of CNS malignant tumor as glioblastomas. |
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Costa, Silvia Lima97970328504http://lattes.cnpq.br/3758218831795212Santos, Balbino Lino dos2020-05-01T19:13:34Z2011-05-26SANTOS, Balbino Lino dos. Avalia??o do potencial antitumoral de flavon?ides polihidroxilados sobre c?lulas de glioblastoma humano. 2011. 145 f. Tese (Doutorado Acad?mico em Biotecnologia)- Universidade Estadual de Feira de Santana, Feira de Santana, 2011.http://tede2.uefs.br:8080/handle/tede/1069In this work, we investigated the effect of polyhydroxilic flavonoids 5,7-dihydroxiflavone (crisin), 3?,4?-dihydroxyflavone, 4?,5,7-trihidroxiflavone (apigenin), 3,4',5,7-tetrahidroxiflavone (kaempferol), 3,3?,4?,5,6-pentahydroxyflavone (quercetin), and 3,3?,4?,5,7-pentahydroxyflavone-3-rutinoside (rutin) on cell viability, phenotypic change, in migratory and invasive capacity in cultured of human glioblastoma multiform cells, using as a model the highly proliferative human cell line GL-15. In a first study we investigated the effects of the flavonoid rutin (3,3',4',5,7-pentahydroxyflavone-3-rutinoside) on growth, viability and morphology of glioblastoma cells. We observed that rutin (50-100 ?M) reduced proliferation and viability of GL-15 cells, leading to decreased levels of ERK1/2 phosphorylation (P-ERK1/2) and accumulation of cells in the G2 phase of the cell cycle. On the other hand, 87.4% of GL-15 cells exposed to 100 ?M rutin entered apoptosis, as revealed by flow cytometry after AnnexinV/PI staining. Nuclear condensation and DNA fragmentation were also observed, further confirming that apoptosis had occurred. Moreover, the remaining cells that were treated with 50 ?M rutin presented a morphological pattern of astroglial differentiation in culture, characterised by a condensed cell body and thin processes with over expression of GFAP. In second study, we investigated the effects of rutin and the others polyhydroxylated flavonoids on viability, morphology, and structure of GL-15 gliobastoma cells, and also the effects on regulation of elements involved in cellular invasion, as cell migration, and expression of MEC, MMPs, and CX43. We observed that, measuring mitochondrial metabolism through MTT-teste, that flavonoids chrysin, apigenin and 3',4'-dihydroxyflavone induced a significative reduction in viability GL-15 cells, besides ultrastructural features of apoptosis. Flavonoids tested also induced morphological changes in GL-15 cells, which acquired a phenotype pattern of astrocytic differentiation, characterized by the presence of a condensed cell body and thin and long cellular processes, expressing GFAP. Scanning electron microscopy showed that flavonoids induced a reduction in filopodia-like structures on the cell surface of GL-15 cells. We found that flavonoids induced a delay in the migration capacity of glioblastoma cells, after the first 12 h after treatment, and cells exhibited increase in intra and extracellular expression fibronectin, and mainly intracellular expression of laminin. Moreover, we also observed that flavonoids induced reduction on MMP-2 expression and MMP activity, and a reduction on Cx43 expression after treatment with rutin. Taken together, these finds show that rutin and polyhydroxylated flavonoids can inhibit the growth, induce morphological changes or apoptosis, and regulate the expression of components involved in tumor cell migration and invasion, these molecules may be considered as potential adjuvants for therapy of CNS malignant tumor as glioblastomas.Neste trabalho objetivamos investigar propriedades antitumorais de flavon?ides polihidroxilados 5,7-dihidroxiflavona (crisina), 3?,4?-dihidroxiflavona, 4?,5,7-trihidroxiflavona (apigenina), 3,4',5,7-tetrahidroxiflavona (kaempferol), 3,3?,4?,5,6-pentahidroxiflavona (quercetina), e 3-O-rutinosideo de 3,3?,4?,5,7-pentahidroxiflavona (rutina) em c?lulas de glioblastoma multiforme humano, usando como modelo a linhagem de c?lulas GL-15. Em um primeiro estudo, investigamos o efeito do flavon?ide rutina em c?lulas GL-15. Foi observado que rutina (50-100 ?M) reduziu a prolifera??o e a viabilidade de c?lulas GL-15, bem como os n?veis de express?o de ERK1/2 fosforilada (P-ERK 1/2), e ac?mulo das c?lulas na fase G2 do ciclo celular. Por outro lado, 87,4% das c?lulas expostas a 100 ?M de rutina entraram em apoptose, como revelado pela citometria de fluxo, ap?s marca??o com Anexina V/PI. Condensa??o nuclear e a fragmenta??o de DNA tamb?m foram observados, confirmando a ocorr?ncia de apoptose. Al?m disso, as c?lulas remanescentes tratadas com 50 ?M de rutina apresentaram um padr?o morfol?gico de diferencia??o astroglial em cultura, caracterizada pela presen?a de um corpo celular condensado e finos processos com express?o elevada de GFAP. Em um segundo estudo, investigamos o efeito de flavon?ides polihidroxilados na viabilidade celular, modifica??o fenot?pica e na capacidade invasiva e migrat?ria em cultura de c?lulas GL-15. N?s observamos que os flavon?ides crisina, apigenina e 3?,4?-dihidroxiflavona induziram uma significativa redu??o na viabilidade das c?lulas ap?s 48 h de tratamento, al?m de mudan?as ultraestruturais indicativas de apoptose. Os flavonoides avaliados tamb?m mostraram serem morfog?nicos para c?lulas GL-15, induzindo um fen?tipo com padr?o de diferencia??o astroglial, caracterizada pela presen?a de um corpo celular condensado e finos processos citoplasm?ticos, com express?o de GFAP. A an?lise por microscopia eletr?nica de varredura tamb?m revelou uma redu??o de estruturas tipo filopodias na superf?cie celular, ap?s tratamento com os flavon?ides em estudo. Observamos que os flavon?ides induziram um retardo na migra??o das c?lulas GL-15 em ensaios de migra??o ap?s as primeiras 12 h de tratamento, bem como regularam a express?o de prote?nas componentes da MEC, sendo observada marca??o intra e extracelular para a fibronectina e marca??o predominantemente intracelular para e laminina. Podemos tamb?m evidenciar que todos os flavonoides testados induziram uma redu??o na express?o e na atividade de MMPs, e que a express?o de CX43 foi reduzida ap?s tratamento com rutina. Devido ? capacidade de induzir a diferencia??o, inibir migra??o celular e induzir a apoptose em cultura de c?lulas de glioblastoma humano, flavon?ides polihidroxilados podem ser considerados como potentes candidatos para o tratamento de gliomas malignos. O conjunto dos resultados deste estudo, que demonstram que a rutina e flavon?ides polihidroxilados possuem capacidade de induzir a diferencia??o, inibir migra??o celular e induzir a apoptose em cultura de c?lulas de glioblastoma humano, sugere flavonoides como potentes candidatos a adjuvantes para o tratamento de tumores cerebais malignos como glioblastoma multiforme.Submitted by Ricardo Cedraz Duque Moliterno (ricardo.moliterno@uefs.br) on 2020-05-01T19:13:34Z No. of bitstreams: 1 TESE - Vers?o Final - Balbino Lino.pdf: 3306573 bytes, checksum: 2f7d895419555055c040237bfb214b96 (MD5)Made available in DSpace on 2020-05-01T19:13:34Z (GMT). No. of bitstreams: 1 TESE - Vers?o Final - Balbino Lino.pdf: 3306573 bytes, checksum: 2f7d895419555055c040237bfb214b96 (MD5) Previous issue date: 2011-05-26application/pdfporUniversidade Estadual de Feira de SantanaDoutorado Acad?mico em BiotecnologiaUEFSBrasilDEPARTAMENTO DE CI?NCIAS BIOL?GICASFlavonoidesGlioblastomasApoptoseDiferencia??oMECMMPFlavonoidsGlioblastomaApoptosisDifferentiationCIENCIAS BIOLOGICASCIENCIAS BIOLOGICAS::BIOLOGIA GERALAvalia??o do potencial antitumoral de flavon?ides polihidroxilados sobre c?lulas de glioblastoma humanoinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis-68152692297897915436006006006005026123383450589282-3439178843068202161-1634559385931244697info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UEFSinstname:Universidade Estadual de Feira de Santana (UEFS)instacron:UEFSORIGINALTESE - Vers?o Final - Balbino Lino.pdfTESE - Vers?o Final - Balbino Lino.pdfapplication/pdf3306573http://tede2.uefs.br:8080/bitstream/tede/1069/2/TESE+-+Vers%C3%A3o+Final+-+Balbino+Lino.pdf2f7d895419555055c040237bfb214b96MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82089http://tede2.uefs.br:8080/bitstream/tede/1069/1/license.txt7b5ba3d2445355f386edab96125d42b7MD51tede/10692020-05-01 16:13:34.253oai:tede2.uefs.br:8080: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Biblioteca Digital de Teses e Dissertaçõeshttp://tede2.uefs.br:8080/PUBhttp://tede2.uefs.br:8080/oai/requestbcuefs@uefs.br|| bcref@uefs.br||bcuefs@uefs.bropendoar:2020-05-01T19:13:34Biblioteca Digital de Teses e Dissertações da UEFS - Universidade Estadual de Feira de Santana (UEFS)false |
dc.title.por.fl_str_mv |
Avalia??o do potencial antitumoral de flavon?ides polihidroxilados sobre c?lulas de glioblastoma humano |
title |
Avalia??o do potencial antitumoral de flavon?ides polihidroxilados sobre c?lulas de glioblastoma humano |
spellingShingle |
Avalia??o do potencial antitumoral de flavon?ides polihidroxilados sobre c?lulas de glioblastoma humano Santos, Balbino Lino dos Flavonoides Glioblastomas Apoptose Diferencia??o MEC MMP Flavonoids Glioblastoma Apoptosis Differentiation CIENCIAS BIOLOGICAS CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
title_short |
Avalia??o do potencial antitumoral de flavon?ides polihidroxilados sobre c?lulas de glioblastoma humano |
title_full |
Avalia??o do potencial antitumoral de flavon?ides polihidroxilados sobre c?lulas de glioblastoma humano |
title_fullStr |
Avalia??o do potencial antitumoral de flavon?ides polihidroxilados sobre c?lulas de glioblastoma humano |
title_full_unstemmed |
Avalia??o do potencial antitumoral de flavon?ides polihidroxilados sobre c?lulas de glioblastoma humano |
title_sort |
Avalia??o do potencial antitumoral de flavon?ides polihidroxilados sobre c?lulas de glioblastoma humano |
author |
Santos, Balbino Lino dos |
author_facet |
Santos, Balbino Lino dos |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Costa, Silvia Lima |
dc.contributor.authorID.fl_str_mv |
97970328504 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/3758218831795212 |
dc.contributor.author.fl_str_mv |
Santos, Balbino Lino dos |
contributor_str_mv |
Costa, Silvia Lima |
dc.subject.por.fl_str_mv |
Flavonoides Glioblastomas Apoptose Diferencia??o MEC MMP |
topic |
Flavonoides Glioblastomas Apoptose Diferencia??o MEC MMP Flavonoids Glioblastoma Apoptosis Differentiation CIENCIAS BIOLOGICAS CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
dc.subject.eng.fl_str_mv |
Flavonoids Glioblastoma Apoptosis Differentiation |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
description |
In this work, we investigated the effect of polyhydroxilic flavonoids 5,7-dihydroxiflavone (crisin), 3?,4?-dihydroxyflavone, 4?,5,7-trihidroxiflavone (apigenin), 3,4',5,7-tetrahidroxiflavone (kaempferol), 3,3?,4?,5,6-pentahydroxyflavone (quercetin), and 3,3?,4?,5,7-pentahydroxyflavone-3-rutinoside (rutin) on cell viability, phenotypic change, in migratory and invasive capacity in cultured of human glioblastoma multiform cells, using as a model the highly proliferative human cell line GL-15. In a first study we investigated the effects of the flavonoid rutin (3,3',4',5,7-pentahydroxyflavone-3-rutinoside) on growth, viability and morphology of glioblastoma cells. We observed that rutin (50-100 ?M) reduced proliferation and viability of GL-15 cells, leading to decreased levels of ERK1/2 phosphorylation (P-ERK1/2) and accumulation of cells in the G2 phase of the cell cycle. On the other hand, 87.4% of GL-15 cells exposed to 100 ?M rutin entered apoptosis, as revealed by flow cytometry after AnnexinV/PI staining. Nuclear condensation and DNA fragmentation were also observed, further confirming that apoptosis had occurred. Moreover, the remaining cells that were treated with 50 ?M rutin presented a morphological pattern of astroglial differentiation in culture, characterised by a condensed cell body and thin processes with over expression of GFAP. In second study, we investigated the effects of rutin and the others polyhydroxylated flavonoids on viability, morphology, and structure of GL-15 gliobastoma cells, and also the effects on regulation of elements involved in cellular invasion, as cell migration, and expression of MEC, MMPs, and CX43. We observed that, measuring mitochondrial metabolism through MTT-teste, that flavonoids chrysin, apigenin and 3',4'-dihydroxyflavone induced a significative reduction in viability GL-15 cells, besides ultrastructural features of apoptosis. Flavonoids tested also induced morphological changes in GL-15 cells, which acquired a phenotype pattern of astrocytic differentiation, characterized by the presence of a condensed cell body and thin and long cellular processes, expressing GFAP. Scanning electron microscopy showed that flavonoids induced a reduction in filopodia-like structures on the cell surface of GL-15 cells. We found that flavonoids induced a delay in the migration capacity of glioblastoma cells, after the first 12 h after treatment, and cells exhibited increase in intra and extracellular expression fibronectin, and mainly intracellular expression of laminin. Moreover, we also observed that flavonoids induced reduction on MMP-2 expression and MMP activity, and a reduction on Cx43 expression after treatment with rutin. Taken together, these finds show that rutin and polyhydroxylated flavonoids can inhibit the growth, induce morphological changes or apoptosis, and regulate the expression of components involved in tumor cell migration and invasion, these molecules may be considered as potential adjuvants for therapy of CNS malignant tumor as glioblastomas. |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011-05-26 |
dc.date.accessioned.fl_str_mv |
2020-05-01T19:13:34Z |
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.citation.fl_str_mv |
SANTOS, Balbino Lino dos. Avalia??o do potencial antitumoral de flavon?ides polihidroxilados sobre c?lulas de glioblastoma humano. 2011. 145 f. Tese (Doutorado Acad?mico em Biotecnologia)- Universidade Estadual de Feira de Santana, Feira de Santana, 2011. |
dc.identifier.uri.fl_str_mv |
http://tede2.uefs.br:8080/handle/tede/1069 |
identifier_str_mv |
SANTOS, Balbino Lino dos. Avalia??o do potencial antitumoral de flavon?ides polihidroxilados sobre c?lulas de glioblastoma humano. 2011. 145 f. Tese (Doutorado Acad?mico em Biotecnologia)- Universidade Estadual de Feira de Santana, Feira de Santana, 2011. |
url |
http://tede2.uefs.br:8080/handle/tede/1069 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.program.fl_str_mv |
-6815269229789791543 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 |
dc.relation.department.fl_str_mv |
5026123383450589282 |
dc.relation.cnpq.fl_str_mv |
-3439178843068202161 -1634559385931244697 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Estadual de Feira de Santana |
dc.publisher.program.fl_str_mv |
Doutorado Acad?mico em Biotecnologia |
dc.publisher.initials.fl_str_mv |
UEFS |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
DEPARTAMENTO DE CI?NCIAS BIOL?GICAS |
publisher.none.fl_str_mv |
Universidade Estadual de Feira de Santana |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da UEFS instname:Universidade Estadual de Feira de Santana (UEFS) instacron:UEFS |
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Universidade Estadual de Feira de Santana (UEFS) |
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UEFS |
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UEFS |
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Biblioteca Digital de Teses e Dissertações da UEFS |
collection |
Biblioteca Digital de Teses e Dissertações da UEFS |
bitstream.url.fl_str_mv |
http://tede2.uefs.br:8080/bitstream/tede/1069/2/TESE+-+Vers%C3%A3o+Final+-+Balbino+Lino.pdf http://tede2.uefs.br:8080/bitstream/tede/1069/1/license.txt |
bitstream.checksum.fl_str_mv |
2f7d895419555055c040237bfb214b96 7b5ba3d2445355f386edab96125d42b7 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da UEFS - Universidade Estadual de Feira de Santana (UEFS) |
repository.mail.fl_str_mv |
bcuefs@uefs.br|| bcref@uefs.br||bcuefs@uefs.br |
_version_ |
1796793641147039744 |