Potencial quimioterápico da berberina em linhagens celulares de glioblastoma multiforme comparado ao tratamento padrão

Bibliographic Details
Main Author: Bortoluzzi, Luisa Donato
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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spelling 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
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||manancial@ufsm.br
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