Potencial quimioterápico da berberina em linhagens celulares de glioblastoma multiforme comparado ao tratamento padrão
Main Author: | |
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Publication Date: | 2025 |
Format: | Master thesis |
Language: | por |
Source: | Manancial - Repositório Digital da UFSM |
dARK ID: | ark:/26339/0013000019682 |
Download full: | http://repositorio.ufsm.br/handle/1/34561 |
Summary: | In Brazil, it is estimated that more than eleven thousand cases of primary central nervous system (CNS) tumors occur each year, with approximately 80% of malignant CNS tumors being gliomas. Glioblastoma multiforme (GBM), a type of glioma, is the most common and lethal malignant brain tumor, leading to a poor prognosis for patients. Due to the low response to conventional treatment with temozolomide (TMZ), the search for new potential drug therapies becomes essential. In this context, berberine (BBR), found in plants of the Berberidaceae family, has emerged as an alternative for GBM treatment due to its antitumor activity and ability to cross the bloodbrain barrier (BBB). However, there is no evaluation of the chronic activity of BBR compared to TMZ, nor whether a synergistic effect exists between the drugs. Therefore, this study evaluated the in vitro chemotherapeutic potential of BBR, both acutely and chronically, in comparison and combination with the drug used in the standard GBM treatment in cell lines sensitive and resistant to this therapy. The results demonstrated that BBR exerts a cytotoxic effect in a dose- and time-dependent manner, being more effective at 50 µM after 72 hours and 7 days. Its combination with TMZ enhanced cytotoxicity, suggesting an additive effect. Additionally, BBR inhibited colony formation, particularly in the A172 cell line, and reduced cell migration, while TMZ alone did not impact the mobility of U138 cells. These findings highlight the potential of BBR as an antitumor agent, especially in combination with TMZ, and emphasize the need for further studies to elucidate its molecular mechanisms and in vivo efficacy. |
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Potencial quimioterápico da berberina em linhagens celulares de glioblastoma multiforme comparado ao tratamento padrãoChemotherapeutic potential of berberine in glioblastoma multiforme cell lines compared to standard treatmentBerberinaCultura celularGlioblastoma multiformePotencial quimioterápicoTemozolomidaBerberineCell cultureGlioblastoma multiformeChemotherapeutic potentialTemozolomideCNPQ::CIENCIAS DA SAUDE::FARMACIAIn Brazil, it is estimated that more than eleven thousand cases of primary central nervous system (CNS) tumors occur each year, with approximately 80% of malignant CNS tumors being gliomas. Glioblastoma multiforme (GBM), a type of glioma, is the most common and lethal malignant brain tumor, leading to a poor prognosis for patients. Due to the low response to conventional treatment with temozolomide (TMZ), the search for new potential drug therapies becomes essential. In this context, berberine (BBR), found in plants of the Berberidaceae family, has emerged as an alternative for GBM treatment due to its antitumor activity and ability to cross the bloodbrain barrier (BBB). However, there is no evaluation of the chronic activity of BBR compared to TMZ, nor whether a synergistic effect exists between the drugs. Therefore, this study evaluated the in vitro chemotherapeutic potential of BBR, both acutely and chronically, in comparison and combination with the drug used in the standard GBM treatment in cell lines sensitive and resistant to this therapy. The results demonstrated that BBR exerts a cytotoxic effect in a dose- and time-dependent manner, being more effective at 50 µM after 72 hours and 7 days. Its combination with TMZ enhanced cytotoxicity, suggesting an additive effect. Additionally, BBR inhibited colony formation, particularly in the A172 cell line, and reduced cell migration, while TMZ alone did not impact the mobility of U138 cells. These findings highlight the potential of BBR as an antitumor agent, especially in combination with TMZ, and emphasize the need for further studies to elucidate its molecular mechanisms and in vivo efficacy.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESNo Brasil, estima-se que ocorram mais de onze mil casos de tumores primários do sistema nervoso central (SNC) por ano e aproximadamente 80% dos tumores malignos do SNC são gliomas. O glioblastoma multiforme (GBM), um tipo de glioma, é o tumor cerebral maligno mais comum e letal, levando os pacientes a um péssimo prognóstico. Devido à baixa resposta ao tratamento convencional com temozolomida (TMZ), a pesquisa por novas possíveis terapias medicamentosas torna-se indispensável. Neste contexto, a berberina (BBR), encontrada em plantas da família Berberidaceae, tem surgido como uma alternativa para o tratamento do GBM por apresentar atividade antitumoral e atravessar a barreira hematoencefálica (BHE). Entretanto, não existe avaliação da atividade crônica da BBR em comparação com a TMZ, nem se existe efeito sinérgico entre as drogas. Diante disso, o presente trabalho avaliou o potencial quimioterápico da BBR in vitro, de forma aguda e crônica, em comparação e em combinação com a droga utilizada no tratamento padrão de GBM em linhagens sensíveis e resistentes a tal terapia. Os resultados demonstraram que a BBR apresenta efeito citotóxico de maneira dose- e tempo-dependente, sendo mais eficaz em 50 µM após 72 horas e 7 dias. Sua associação com a TMZ intensificou a citotoxicidade, sugerindo um efeito aditivo. Além disso, a BBR inibiu a formação de colônias, especialmente na linhagem A172, e reduziu a migração celular, enquanto a TMZ isolada não impactou a mobilidade das células U138. Esses resultados destacam o potencial da BBR como agente antitumoral, principalmente em combinação com a TMZ, e ressaltam a necessidade de estudos adicionais para esclarecer seus mecanismos moleculares e sua eficácia in vivo.Universidade Federal de Santa MariaBrasilFarmáciaUFSMPrograma de Pós-Graduação em Ciências FarmacêuticasCentro de Ciências da SaúdePillat, Micheli Mainardihttp://lattes.cnpq.br/5712882578120587Lenz, Luana SuélingVidal, TaísLameu, ClaudianaBortoluzzi, Luisa Donato2025-03-25T11:44:49Z2025-03-25T11:44:49Z2025-02-24info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/34561ark:/26339/0013000019682porAttribution-NonCommercial-NoDerivatives 4.0 Internationalinfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2025-03-25T11:44:49Zoai:repositorio.ufsm.br:1/34561Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/PUBhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.com||manancial@ufsm.bropendoar:2025-03-25T11:44:49Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Potencial quimioterápico da berberina em linhagens celulares de glioblastoma multiforme comparado ao tratamento padrão Chemotherapeutic potential of berberine in glioblastoma multiforme cell lines compared to standard treatment |
title |
Potencial quimioterápico da berberina em linhagens celulares de glioblastoma multiforme comparado ao tratamento padrão |
spellingShingle |
Potencial quimioterápico da berberina em linhagens celulares de glioblastoma multiforme comparado ao tratamento padrão Bortoluzzi, Luisa Donato Berberina Cultura celular Glioblastoma multiforme Potencial quimioterápico Temozolomida Berberine Cell culture Glioblastoma multiforme Chemotherapeutic potential Temozolomide CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Potencial quimioterápico da berberina em linhagens celulares de glioblastoma multiforme comparado ao tratamento padrão |
title_full |
Potencial quimioterápico da berberina em linhagens celulares de glioblastoma multiforme comparado ao tratamento padrão |
title_fullStr |
Potencial quimioterápico da berberina em linhagens celulares de glioblastoma multiforme comparado ao tratamento padrão |
title_full_unstemmed |
Potencial quimioterápico da berberina em linhagens celulares de glioblastoma multiforme comparado ao tratamento padrão |
title_sort |
Potencial quimioterápico da berberina em linhagens celulares de glioblastoma multiforme comparado ao tratamento padrão |
author |
Bortoluzzi, Luisa Donato |
author_facet |
Bortoluzzi, Luisa Donato |
author_role |
author |
dc.contributor.none.fl_str_mv |
Pillat, Micheli Mainardi http://lattes.cnpq.br/5712882578120587 Lenz, Luana Suéling Vidal, Taís Lameu, Claudiana |
dc.contributor.author.fl_str_mv |
Bortoluzzi, Luisa Donato |
dc.subject.por.fl_str_mv |
Berberina Cultura celular Glioblastoma multiforme Potencial quimioterápico Temozolomida Berberine Cell culture Glioblastoma multiforme Chemotherapeutic potential Temozolomide CNPQ::CIENCIAS DA SAUDE::FARMACIA |
topic |
Berberina Cultura celular Glioblastoma multiforme Potencial quimioterápico Temozolomida Berberine Cell culture Glioblastoma multiforme Chemotherapeutic potential Temozolomide CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
In Brazil, it is estimated that more than eleven thousand cases of primary central nervous system (CNS) tumors occur each year, with approximately 80% of malignant CNS tumors being gliomas. Glioblastoma multiforme (GBM), a type of glioma, is the most common and lethal malignant brain tumor, leading to a poor prognosis for patients. Due to the low response to conventional treatment with temozolomide (TMZ), the search for new potential drug therapies becomes essential. In this context, berberine (BBR), found in plants of the Berberidaceae family, has emerged as an alternative for GBM treatment due to its antitumor activity and ability to cross the bloodbrain barrier (BBB). However, there is no evaluation of the chronic activity of BBR compared to TMZ, nor whether a synergistic effect exists between the drugs. Therefore, this study evaluated the in vitro chemotherapeutic potential of BBR, both acutely and chronically, in comparison and combination with the drug used in the standard GBM treatment in cell lines sensitive and resistant to this therapy. The results demonstrated that BBR exerts a cytotoxic effect in a dose- and time-dependent manner, being more effective at 50 µM after 72 hours and 7 days. Its combination with TMZ enhanced cytotoxicity, suggesting an additive effect. Additionally, BBR inhibited colony formation, particularly in the A172 cell line, and reduced cell migration, while TMZ alone did not impact the mobility of U138 cells. These findings highlight the potential of BBR as an antitumor agent, especially in combination with TMZ, and emphasize the need for further studies to elucidate its molecular mechanisms and in vivo efficacy. |
publishDate |
2025 |
dc.date.none.fl_str_mv |
2025-03-25T11:44:49Z 2025-03-25T11:44:49Z 2025-02-24 |
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/1/34561 |
dc.identifier.dark.fl_str_mv |
ark:/26339/0013000019682 |
url |
http://repositorio.ufsm.br/handle/1/34561 |
identifier_str_mv |
ark:/26339/0013000019682 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International |
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 Farmácia UFSM Programa de Pós-Graduação em Ciências Farmacêuticas Centro de Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Farmácia UFSM Programa de Pós-Graduação em Ciências Farmacêuticas Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
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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||manancial@ufsm.br |
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1838454043005943808 |