Guaraná, um fruto ultracafeinado, apresenta efeito in vitro antitumoral e na atividade quimioterápica em células de câncer colorretal e de mama
Autor(a) principal: | |
---|---|
Data de Publicação: | 2016 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/17967 |
Resumo: | Introduction: Colorectal (CRC) and breast cancer are considered the most incidents in the entire world. Antioxidant extracts are largely used to prevent mutations and neoplasia as well as in patients undergoing the chemotherapy treatment, such as the Paullinia cupana (guaraná). A previous in vitro study suggested that guaraná could have antitumor action against the breast cancer as well as increase anti-proliferative sensitivity of eight different drugs. However, there are two questions have not yet been clarified: whether this same effect occur in the CRC and which would be the causal mechanism that guaraná act in tumoral cells. There are many biologics proprieties of guaraná published in the literature. Considering that, guaraná could present the antitumor activity by modulations in the Mammalian Target of Rapamycin (mTOR) and Mitogen-activated Protein Kinase (MAPKs) pathways. Objective: the aim of this study was to analyze the antitumor in vitro effect of the hydroalcoholic guaraná end its main bioactives molecules in the CRC and in the breast cancer cells. The action in the chemotherapic activity of this extract also was investigated in the CRC cells. Besides, the cytotoxicity of guaraná was analyzed in the healthy cells. Methods: The study was performed using two cell lines HT-29 and MCF-7, CRC and breast cancer, respectively. The cell line HT-29 was exposed to different concentrations of guaraná, as well as its main bioactive molecules, caffeine, theobromine and catechin. Guaraná effect in chemotherapy activity was measured by HT-29 exposure to the better antitumor guaraná concentrations, besides its bioactive compounds in the addiction of Oxaliplatin. Although, the cell line MCF-7 was exposed to different concentrations of guaraná and only the molecule more prevalent found in the extract, the caffeine. Some parameters were analyzed, such as cellular proliferation and viability, cell cycle arrests, apoptotic pathway activation, cancer association proteins expression, modulations in mTOR and MAPKs pathways. These parameters were measured by spectrophotometric, fluorimetric and molecular analysis. Moreover, cytotoxicity parameters of the extract were performed in healthy cells, using fibroblast lineage (HFF-1) and peripheral blood mononuclear cells (PBMCs). Results: Guaraná exhibited antitumor activity in some concentrations (0.1; 1; 10; 30; 100 e 300 μg/mL), as well as its bioactive compounds in the both cell linage tested, HT-29 and MCF-7. Besides, the action of Oxaliplatin was potentiated in some concentrations of guaraná (30; 100 e 300 μg/mL) and its bioactive molecules on HT-29. The guaraná did not negatively interfere in the action of Oxaliplatin. Guaraná and caffeine inhibited proteins in MAPKs and mTOR pathways on MCF-7. However, the guaraná only inhibited the mTOR pathway and the caffeine did not present effect. The guaraná did not present cytotoxic effect on healthy cells. Therefore, the results suggested that the guaraná could be a potential carcinogenic agent besides it could be used as a supplement during the chemotherapic treatment for potentiating the antitumor response and decrease the tumor cells resistance. |
id |
UFSM_15bbb1e5dd2c3ac33567d4cc3222e863 |
---|---|
oai_identifier_str |
oai:repositorio.ufsm.br:1/17967 |
network_acronym_str |
UFSM |
network_name_str |
Manancial - Repositório Digital da UFSM |
repository_id_str |
|
spelling |
Guaraná, um fruto ultracafeinado, apresenta efeito in vitro antitumoral e na atividade quimioterápica em células de câncer colorretal e de mamaGuaraná, a highly caffeinated fruit, has in vitro antitumor effect and in the chemotherapic activit on colorectal and on breast cancerGuaranáCafeínaCâncer colorretalCâncer de mamaAtividade antitumoralSinergismo quimioterápicoCaffeineColorectal cancerBreast cancerAntitumor activitySynergism chemotherapyCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAIntroduction: Colorectal (CRC) and breast cancer are considered the most incidents in the entire world. Antioxidant extracts are largely used to prevent mutations and neoplasia as well as in patients undergoing the chemotherapy treatment, such as the Paullinia cupana (guaraná). A previous in vitro study suggested that guaraná could have antitumor action against the breast cancer as well as increase anti-proliferative sensitivity of eight different drugs. However, there are two questions have not yet been clarified: whether this same effect occur in the CRC and which would be the causal mechanism that guaraná act in tumoral cells. There are many biologics proprieties of guaraná published in the literature. Considering that, guaraná could present the antitumor activity by modulations in the Mammalian Target of Rapamycin (mTOR) and Mitogen-activated Protein Kinase (MAPKs) pathways. Objective: the aim of this study was to analyze the antitumor in vitro effect of the hydroalcoholic guaraná end its main bioactives molecules in the CRC and in the breast cancer cells. The action in the chemotherapic activity of this extract also was investigated in the CRC cells. Besides, the cytotoxicity of guaraná was analyzed in the healthy cells. Methods: The study was performed using two cell lines HT-29 and MCF-7, CRC and breast cancer, respectively. The cell line HT-29 was exposed to different concentrations of guaraná, as well as its main bioactive molecules, caffeine, theobromine and catechin. Guaraná effect in chemotherapy activity was measured by HT-29 exposure to the better antitumor guaraná concentrations, besides its bioactive compounds in the addiction of Oxaliplatin. Although, the cell line MCF-7 was exposed to different concentrations of guaraná and only the molecule more prevalent found in the extract, the caffeine. Some parameters were analyzed, such as cellular proliferation and viability, cell cycle arrests, apoptotic pathway activation, cancer association proteins expression, modulations in mTOR and MAPKs pathways. These parameters were measured by spectrophotometric, fluorimetric and molecular analysis. Moreover, cytotoxicity parameters of the extract were performed in healthy cells, using fibroblast lineage (HFF-1) and peripheral blood mononuclear cells (PBMCs). Results: Guaraná exhibited antitumor activity in some concentrations (0.1; 1; 10; 30; 100 e 300 μg/mL), as well as its bioactive compounds in the both cell linage tested, HT-29 and MCF-7. Besides, the action of Oxaliplatin was potentiated in some concentrations of guaraná (30; 100 e 300 μg/mL) and its bioactive molecules on HT-29. The guaraná did not negatively interfere in the action of Oxaliplatin. Guaraná and caffeine inhibited proteins in MAPKs and mTOR pathways on MCF-7. However, the guaraná only inhibited the mTOR pathway and the caffeine did not present effect. The guaraná did not present cytotoxic effect on healthy cells. Therefore, the results suggested that the guaraná could be a potential carcinogenic agent besides it could be used as a supplement during the chemotherapic treatment for potentiating the antitumor response and decrease the tumor cells resistance.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESIntrodução: Dentre os cânceres mais incidentes destacam-se o câncer colorretal (CCR) e o de mama. Extratos antioxidantes são amplamente utilizados, não apenas para prevenir neoplasias, mas ainda durante o tratamento quimioterápico, como é o caso da Paullinia cupana (guaraná). Um estudo in vitro prévio sugeriu que o guaraná poderia ter ação antitumoral contra o câncer de mama, potencializando ainda o efeito de oito tipos de quimioterápicos. Entretanto, se esse efeito também ocorre no CCR e qual seria o mecanismo causal pelo qual o guaraná age nas células tumorais são questões não esclarecidas, até o presente momento. Considerando as propriedades biológicas do guaraná, pode-se inferir que o mesmo teria efeito antitumoral via modulação das rotas da Proteína Alvo da Rapamicina em Mamíferos (mTOR) e das Proteínas Quinases Ativadas por Mitógenos (MAPKs). Objetivo: Avaliar o efeito antitumoral in vitro do extrato hidroalcóolico do guaraná e das suas principais moléculas bioativas nas células de CCR e de mama, assim como, na atividade quimioterápica em células de CCR. Métodos: o estudo foi realizado em duas linhagens celulares HT-29 e MCF-7, para CCR e câncer de mama, respectivamente. A linhagem celular HT-29 foi exposta a diferentes concentrações de guaraná, bem como, às suas principais moléculas bioativas, cafeína, teobromina e catequina. Para a avaliação do efeito do guaraná na atividade quimioterápica, as células HT- 29 foram expostas a concentrações antitumorais do guaraná mais eficazes, bem como, a dos seus compostos bioativos em associação ao quimioterápico Oxaliplatina. Já a linhagem celular MCF-7 foi exposta a diferentes concentrações de guaraná e apenas a sua molécula biotiva mais prevalentes, a cafeína. Foram avaliados parâmetros de viabilidade e proliferação celular, alterações no ciclo celular, ativação da via apoptótica, expressão de proteínas associadas ao câncer, modulações na rota da mTOR e das MAPKs, via análises espectrofotométricas, fluorimétricas e moleculares. Além disso, parâmetros de citotoxicidade do extrato foram realizados em células saudáveis, usando linhagem de fibroblastos (HFF-1) e Células Mononucleares do Sangue Periférico (CMSPs). Resultados: O guaraná exibiu atividade antitumoral em determinadas concentrações (0.1; 1; 10; 30; 100 e 300 μg/mL), assim como, as suas moléculas bioativas, tanto em HT-29 quanto em MCF-7. Além disso, foi averiguado um aumento da ação do fármaco em algumas concentrações (30; 100 e 300 μg/mL) do guaraná e seus bioativos em células HT-29. O guaraná não interferiu negativamente na ação da Oxaliplatina. O guaraná e a cafeína inibiram proteínas das vias MAPKs e mTOR nas células MCF-7. Entretanto, nas células HT-29 o guaraná apenas inibiu a rota da mTOR, já a cafeína não apresentou nenhum efeito significativo. Como esperado, o guaraná não exibiu citotoxicidade a células saudáveis. Portanto, os resultados sugeriram que o guaraná apresentou atividade antitumoral contra células de câncer de mama e CCR, e ainda, potencializou a ação da Oxaliplatina em células de CCR. Assim, o guaraná poderia ser usado como um suplemento durante o tratamento quimioterápico, a fim de potencializar resposta antitumoral e assim, diminuir a resistência dessas células.Universidade Federal de Santa MariaBrasilBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaCentro de Ciências Naturais e ExatasCruz, Ivana Beatrice Mânica dahttp://lattes.cnpq.br/3426369324110716Bica, Claudia Giulianohttp://lattes.cnpq.br/4488122519766245Wagner, Glauberhttp://lattes.cnpq.br/8417542717418294Santos, Roberto Christ Viannahttp://lattes.cnpq.br/9176719594431835Cadoná, Francine Carla2019-08-19T21:18:08Z2019-08-19T21:18:08Z2016-07-15info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/17967porAttribution-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:UFSM2019-08-20T06:02:22Zoai:repositorio.ufsm.br:1/17967Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2019-08-20T06:02:22Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Guaraná, um fruto ultracafeinado, apresenta efeito in vitro antitumoral e na atividade quimioterápica em células de câncer colorretal e de mama Guaraná, a highly caffeinated fruit, has in vitro antitumor effect and in the chemotherapic activit on colorectal and on breast cancer |
title |
Guaraná, um fruto ultracafeinado, apresenta efeito in vitro antitumoral e na atividade quimioterápica em células de câncer colorretal e de mama |
spellingShingle |
Guaraná, um fruto ultracafeinado, apresenta efeito in vitro antitumoral e na atividade quimioterápica em células de câncer colorretal e de mama Cadoná, Francine Carla Guaraná Cafeína Câncer colorretal Câncer de mama Atividade antitumoral Sinergismo quimioterápico Caffeine Colorectal cancer Breast cancer Antitumor activity Synergism chemotherapy CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Guaraná, um fruto ultracafeinado, apresenta efeito in vitro antitumoral e na atividade quimioterápica em células de câncer colorretal e de mama |
title_full |
Guaraná, um fruto ultracafeinado, apresenta efeito in vitro antitumoral e na atividade quimioterápica em células de câncer colorretal e de mama |
title_fullStr |
Guaraná, um fruto ultracafeinado, apresenta efeito in vitro antitumoral e na atividade quimioterápica em células de câncer colorretal e de mama |
title_full_unstemmed |
Guaraná, um fruto ultracafeinado, apresenta efeito in vitro antitumoral e na atividade quimioterápica em células de câncer colorretal e de mama |
title_sort |
Guaraná, um fruto ultracafeinado, apresenta efeito in vitro antitumoral e na atividade quimioterápica em células de câncer colorretal e de mama |
author |
Cadoná, Francine Carla |
author_facet |
Cadoná, Francine Carla |
author_role |
author |
dc.contributor.none.fl_str_mv |
Cruz, Ivana Beatrice Mânica da http://lattes.cnpq.br/3426369324110716 Bica, Claudia Giuliano http://lattes.cnpq.br/4488122519766245 Wagner, Glauber http://lattes.cnpq.br/8417542717418294 Santos, Roberto Christ Vianna http://lattes.cnpq.br/9176719594431835 |
dc.contributor.author.fl_str_mv |
Cadoná, Francine Carla |
dc.subject.por.fl_str_mv |
Guaraná Cafeína Câncer colorretal Câncer de mama Atividade antitumoral Sinergismo quimioterápico Caffeine Colorectal cancer Breast cancer Antitumor activity Synergism chemotherapy CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
topic |
Guaraná Cafeína Câncer colorretal Câncer de mama Atividade antitumoral Sinergismo quimioterápico Caffeine Colorectal cancer Breast cancer Antitumor activity Synergism chemotherapy CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Introduction: Colorectal (CRC) and breast cancer are considered the most incidents in the entire world. Antioxidant extracts are largely used to prevent mutations and neoplasia as well as in patients undergoing the chemotherapy treatment, such as the Paullinia cupana (guaraná). A previous in vitro study suggested that guaraná could have antitumor action against the breast cancer as well as increase anti-proliferative sensitivity of eight different drugs. However, there are two questions have not yet been clarified: whether this same effect occur in the CRC and which would be the causal mechanism that guaraná act in tumoral cells. There are many biologics proprieties of guaraná published in the literature. Considering that, guaraná could present the antitumor activity by modulations in the Mammalian Target of Rapamycin (mTOR) and Mitogen-activated Protein Kinase (MAPKs) pathways. Objective: the aim of this study was to analyze the antitumor in vitro effect of the hydroalcoholic guaraná end its main bioactives molecules in the CRC and in the breast cancer cells. The action in the chemotherapic activity of this extract also was investigated in the CRC cells. Besides, the cytotoxicity of guaraná was analyzed in the healthy cells. Methods: The study was performed using two cell lines HT-29 and MCF-7, CRC and breast cancer, respectively. The cell line HT-29 was exposed to different concentrations of guaraná, as well as its main bioactive molecules, caffeine, theobromine and catechin. Guaraná effect in chemotherapy activity was measured by HT-29 exposure to the better antitumor guaraná concentrations, besides its bioactive compounds in the addiction of Oxaliplatin. Although, the cell line MCF-7 was exposed to different concentrations of guaraná and only the molecule more prevalent found in the extract, the caffeine. Some parameters were analyzed, such as cellular proliferation and viability, cell cycle arrests, apoptotic pathway activation, cancer association proteins expression, modulations in mTOR and MAPKs pathways. These parameters were measured by spectrophotometric, fluorimetric and molecular analysis. Moreover, cytotoxicity parameters of the extract were performed in healthy cells, using fibroblast lineage (HFF-1) and peripheral blood mononuclear cells (PBMCs). Results: Guaraná exhibited antitumor activity in some concentrations (0.1; 1; 10; 30; 100 e 300 μg/mL), as well as its bioactive compounds in the both cell linage tested, HT-29 and MCF-7. Besides, the action of Oxaliplatin was potentiated in some concentrations of guaraná (30; 100 e 300 μg/mL) and its bioactive molecules on HT-29. The guaraná did not negatively interfere in the action of Oxaliplatin. Guaraná and caffeine inhibited proteins in MAPKs and mTOR pathways on MCF-7. However, the guaraná only inhibited the mTOR pathway and the caffeine did not present effect. The guaraná did not present cytotoxic effect on healthy cells. Therefore, the results suggested that the guaraná could be a potential carcinogenic agent besides it could be used as a supplement during the chemotherapic treatment for potentiating the antitumor response and decrease the tumor cells resistance. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-07-15 2019-08-19T21:18:08Z 2019-08-19T21:18:08Z |
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 |
http://repositorio.ufsm.br/handle/1/17967 |
url |
http://repositorio.ufsm.br/handle/1/17967 |
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 |
_version_ |
1805922168177950720 |