Mecanismo antitumoral da berberina em linhagem de células U87MG de glioblastoma multiforme
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/21404 |
Resumo: | Glioblastoma multiforme (GBM) is the most prevalent tumor among gliomas. GBM cells present high pleomorphism, with undifferentiated cells, with cellular atypia and high mitotic activity, being considered as incurable tumors with the highest mortality rate among brain tumors. Berberine (BBR), an alkaloid isoquinoline, is a compound found in medicinal plants such as Coptis chinensis. Studies have been showed that BBR presents protective activity in mesenchymal cells and neurons, and antitumor properties, such as inhibition of cell proliferation, induction of cell cycle arrest, and apoptosis in breast cancer and hepatocarcinoma. The aim of this study was to investigate the antitumor effects of BBR in the GBM U87MG cells, as well as to identify whether such effects are mediated by oxidative stress and canonical apoptotic pathways. After treatment with several concentrations of BBR (10, 25, 100 and 250μM) for 24, 48 and 72 hours, the samples were analyzed by MTT assay and it was observed that BBR inhibited cell viability of U87MG cells in a concentration- and time-dependent manner. Afterwards, it was observed that BBR, starting at a concentration of 25 μM for 24hs, significantly suppressed proliferation evidenced by flow cytometry techniques, while significantly increased early apoptosis (53.5% ± 11.15 of annexin V+ propidium iodide- cells) compared to untreated cells (7.5% ± 4.6). BBR-induced apoptosis was independent on AMPK activity and did not change caspase 3 and p-p53 levels. Moreover, BBR (25μM / 24h) increased oxidative stress in U87MG cells, evidenced by high levels of reactive oxygen species, TBARS and protein carbonylation. Considering the antitumor effects of BBR in U87MG cells, it is suggest that this compound may be a potential candidate for adjuvant GBM treatment. |
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Mecanismo antitumoral da berberina em linhagem de células U87MG de glioblastoma multiformeAntitumoral mechanism of berberine in glioblastoma multiforme U87MG cellGlioblastoma multiformeBerberinaApoptoseLinhagem celular U87MGBerberineApoptosisU87MG cellCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAGlioblastoma multiforme (GBM) is the most prevalent tumor among gliomas. GBM cells present high pleomorphism, with undifferentiated cells, with cellular atypia and high mitotic activity, being considered as incurable tumors with the highest mortality rate among brain tumors. Berberine (BBR), an alkaloid isoquinoline, is a compound found in medicinal plants such as Coptis chinensis. Studies have been showed that BBR presents protective activity in mesenchymal cells and neurons, and antitumor properties, such as inhibition of cell proliferation, induction of cell cycle arrest, and apoptosis in breast cancer and hepatocarcinoma. The aim of this study was to investigate the antitumor effects of BBR in the GBM U87MG cells, as well as to identify whether such effects are mediated by oxidative stress and canonical apoptotic pathways. After treatment with several concentrations of BBR (10, 25, 100 and 250μM) for 24, 48 and 72 hours, the samples were analyzed by MTT assay and it was observed that BBR inhibited cell viability of U87MG cells in a concentration- and time-dependent manner. Afterwards, it was observed that BBR, starting at a concentration of 25 μM for 24hs, significantly suppressed proliferation evidenced by flow cytometry techniques, while significantly increased early apoptosis (53.5% ± 11.15 of annexin V+ propidium iodide- cells) compared to untreated cells (7.5% ± 4.6). BBR-induced apoptosis was independent on AMPK activity and did not change caspase 3 and p-p53 levels. Moreover, BBR (25μM / 24h) increased oxidative stress in U87MG cells, evidenced by high levels of reactive oxygen species, TBARS and protein carbonylation. Considering the antitumor effects of BBR in U87MG cells, it is suggest that this compound may be a potential candidate for adjuvant GBM treatment.Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqO glioblastoma multiforme (GBM) é o tumor com maior prevalência entre os gliomas. As células do GBM apresentam alto pleomorfismo, com células não diferenciadas, com atipia celular e alta atividade mitótica, sendo considerados tumores incuráveis com a maior taxa de mortalidade entre os tumores encefálicos. A berberina (BBR), um alcalóide isoquinolina, é um composto encontrado em plantas medicinais como Coptis chinensis. A BBR demonstrou ter atividade protetora em células mesenquimais e neurônios, e propriedades antitumorais em células de câncer de mama e hepatocarcinoma, como inibição da proliferação celular, a indução da parada do ciclo celular e apoptose. O objetivo deste estudo foi investigar os efeitos antitumorais da BBR na linhagem celular U87MG de GBM, bem como, identificar se tais efeitos são mediados pelo estresse oxidativo e vias apoptóticas canônicas. Após o tratamento com diferentes concentrações de BBR (10, 25 100 e 250μM), por 24, 48 e 72 horas, as amostras foram analisadas pelo método de MTT, a fim de estimar a viabilidade celular. Este alcalóide significantemente reduziu a viabilidade celular/proliferação das células U87MG de uma maneira dependente da concentração e do tempo. Posteriormente, por meio de análises do ciclo celular, observou-se que concentrações a partir de 25 μM de BBR por apenas 24 horas foram suficientes para suprimir a proliferação celular, evidenciada por citometria de fluxo. Tal concentração e tempo de exposição à BBR também foram capazes de desencadear a apoptose, visto que, observou-se um grande aumento na porcentagem (53,5% ± 11,15) de células em apoptose inicial (células Anexina V+ iodeto de propídio-) comparado a amostras não tratadas (7,5% ± 4,6). A apoptose induzida por BBR foi independente da atividade de AMPK e não envolveu mudanças na expressão de caspase 3 e p-p53. A BBR (25μM/24h) aumentou o estresse oxidativo nas células U87MG, observado pelo aumento nos níveis das espécies reativas de oxigênio, TBARS e carbonilação de proteínas. Portanto, a BBR tem potente efeito indutor da apoptose em U87MG e sugere-se que este composto pode ser um potencial candidato para o tratamento adjuvante do GBM.Universidade Federal de Santa MariaBrasilBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaCentro de Ciências Naturais e ExatasAndrade, Cinthia Melazzo dehttp://lattes.cnpq.br/2886709251370905Pillat, Micheli MainardiCappellari, Angélica ReginaAraújo, Maria do Carmo dos SantosPalma, Taís Vidal2021-07-13T11:47:40Z2021-07-13T11:47:40Z2017-07-31info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/21404porAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2021-09-29T19:47:47Zoai:repositorio.ufsm.br:1/21404Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2021-09-29T19:47:47Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Mecanismo antitumoral da berberina em linhagem de células U87MG de glioblastoma multiforme Antitumoral mechanism of berberine in glioblastoma multiforme U87MG cell |
title |
Mecanismo antitumoral da berberina em linhagem de células U87MG de glioblastoma multiforme |
spellingShingle |
Mecanismo antitumoral da berberina em linhagem de células U87MG de glioblastoma multiforme Palma, Taís Vidal Glioblastoma multiforme Berberina Apoptose Linhagem celular U87MG Berberine Apoptosis U87MG cell CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Mecanismo antitumoral da berberina em linhagem de células U87MG de glioblastoma multiforme |
title_full |
Mecanismo antitumoral da berberina em linhagem de células U87MG de glioblastoma multiforme |
title_fullStr |
Mecanismo antitumoral da berberina em linhagem de células U87MG de glioblastoma multiforme |
title_full_unstemmed |
Mecanismo antitumoral da berberina em linhagem de células U87MG de glioblastoma multiforme |
title_sort |
Mecanismo antitumoral da berberina em linhagem de células U87MG de glioblastoma multiforme |
author |
Palma, Taís Vidal |
author_facet |
Palma, Taís Vidal |
author_role |
author |
dc.contributor.none.fl_str_mv |
Andrade, Cinthia Melazzo de http://lattes.cnpq.br/2886709251370905 Pillat, Micheli Mainardi Cappellari, Angélica Regina Araújo, Maria do Carmo dos Santos |
dc.contributor.author.fl_str_mv |
Palma, Taís Vidal |
dc.subject.por.fl_str_mv |
Glioblastoma multiforme Berberina Apoptose Linhagem celular U87MG Berberine Apoptosis U87MG cell CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
topic |
Glioblastoma multiforme Berberina Apoptose Linhagem celular U87MG Berberine Apoptosis U87MG cell CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Glioblastoma multiforme (GBM) is the most prevalent tumor among gliomas. GBM cells present high pleomorphism, with undifferentiated cells, with cellular atypia and high mitotic activity, being considered as incurable tumors with the highest mortality rate among brain tumors. Berberine (BBR), an alkaloid isoquinoline, is a compound found in medicinal plants such as Coptis chinensis. Studies have been showed that BBR presents protective activity in mesenchymal cells and neurons, and antitumor properties, such as inhibition of cell proliferation, induction of cell cycle arrest, and apoptosis in breast cancer and hepatocarcinoma. The aim of this study was to investigate the antitumor effects of BBR in the GBM U87MG cells, as well as to identify whether such effects are mediated by oxidative stress and canonical apoptotic pathways. After treatment with several concentrations of BBR (10, 25, 100 and 250μM) for 24, 48 and 72 hours, the samples were analyzed by MTT assay and it was observed that BBR inhibited cell viability of U87MG cells in a concentration- and time-dependent manner. Afterwards, it was observed that BBR, starting at a concentration of 25 μM for 24hs, significantly suppressed proliferation evidenced by flow cytometry techniques, while significantly increased early apoptosis (53.5% ± 11.15 of annexin V+ propidium iodide- cells) compared to untreated cells (7.5% ± 4.6). BBR-induced apoptosis was independent on AMPK activity and did not change caspase 3 and p-p53 levels. Moreover, BBR (25μM / 24h) increased oxidative stress in U87MG cells, evidenced by high levels of reactive oxygen species, TBARS and protein carbonylation. Considering the antitumor effects of BBR in U87MG cells, it is suggest that this compound may be a potential candidate for adjuvant GBM treatment. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-07-31 2021-07-13T11:47:40Z 2021-07-13T11:47:40Z |
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 |
http://repositorio.ufsm.br/handle/1/21404 |
url |
http://repositorio.ufsm.br/handle/1/21404 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica Centro de Ciências Naturais e Exatas |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica Centro de Ciências Naturais e Exatas |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
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1805922056004435968 |