Avaliação do efeito radiomodificador do resveratrol sobre células de câncer de mama (MCF-7) irradiadas
Autor(a) principal: | |
---|---|
Data de Publicação: | 2016 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional Manancial UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/18149 |
Resumo: | Malignant neoplasias constitute a public health issue, with around 600 thousand new cases of cancer projected to be diagnosed in Brazil between 2016 and 2017. In this context, breast cancer is the most common type in women, reaching around 28% of Brazilian women. Radiation therapy is a therapeutic modality commonly applied in cases of breast cancer in different stages. However, radioresistance, cutaneous radiation syndrome and the occurrence of new neoplasias in healthy cells are the main side effects of this practice. Therefore, the aim of this work was to assess the potential of resveratrol (RV) as a radiosensitizer radiomodifier on breast cancer cells of the lineage MCF-7. For this end, cells were initially treated with different RV doses (0, 10, 30 and 100μM) for 24 hours and then exposed to ionizing radiation (IR) (0, 1, 2 e 3 grays). The results show that the most cytotoxic treatment combination was 10μM and 3 grays, which were the doses chosen for the additional tests. Cellular death assessment through flow cytometry showed that, in 24 hours cell cultures after IR, necrosis/senescence seem to be related to cytotoxicity, besides the activation of extrinsic apoptosis. This phenomenon was clear when the high activity of caspases 3 and 8, and the low bax/bcl-2 ratio were observed. Tests involving oxidative metabolism show that RV and IR are effective together, causing great oxidative damage in DNA, proteins and cellular lipids, as well as diminishing the activity of the antioxidative enzymes dismutase (SOD) and catalase (CAT). The high expression of p53 indicates not to be primarily related to intrinsic apoptosis, but to be indeed related to the interruption of cell cycle in the S phase, which was observed in 72 hours cellular cultures after IR. Thus, the pro-oxidative condition established by the treatment combination, together with the high level of the p53 expression, allow us to suggest that the significant decrease of cellular proliferation in 72 hours cultures seems to be related to the irreversible growth interruption linked to necrosis/senescence, as well as apoptosis activation. |
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2019-09-05T18:12:12Z2019-09-05T18:12:12Z2016-11-28http://repositorio.ufsm.br/handle/1/18149Malignant neoplasias constitute a public health issue, with around 600 thousand new cases of cancer projected to be diagnosed in Brazil between 2016 and 2017. In this context, breast cancer is the most common type in women, reaching around 28% of Brazilian women. Radiation therapy is a therapeutic modality commonly applied in cases of breast cancer in different stages. However, radioresistance, cutaneous radiation syndrome and the occurrence of new neoplasias in healthy cells are the main side effects of this practice. Therefore, the aim of this work was to assess the potential of resveratrol (RV) as a radiosensitizer radiomodifier on breast cancer cells of the lineage MCF-7. For this end, cells were initially treated with different RV doses (0, 10, 30 and 100μM) for 24 hours and then exposed to ionizing radiation (IR) (0, 1, 2 e 3 grays). The results show that the most cytotoxic treatment combination was 10μM and 3 grays, which were the doses chosen for the additional tests. Cellular death assessment through flow cytometry showed that, in 24 hours cell cultures after IR, necrosis/senescence seem to be related to cytotoxicity, besides the activation of extrinsic apoptosis. This phenomenon was clear when the high activity of caspases 3 and 8, and the low bax/bcl-2 ratio were observed. Tests involving oxidative metabolism show that RV and IR are effective together, causing great oxidative damage in DNA, proteins and cellular lipids, as well as diminishing the activity of the antioxidative enzymes dismutase (SOD) and catalase (CAT). The high expression of p53 indicates not to be primarily related to intrinsic apoptosis, but to be indeed related to the interruption of cell cycle in the S phase, which was observed in 72 hours cellular cultures after IR. Thus, the pro-oxidative condition established by the treatment combination, together with the high level of the p53 expression, allow us to suggest that the significant decrease of cellular proliferation in 72 hours cultures seems to be related to the irreversible growth interruption linked to necrosis/senescence, as well as apoptosis activation.As neoplasias malignas constituem um problema de saúde pública, sendo que, cerca de 600 mil novos casos de câncer estão previstos para o Brasil no biênio 2016-2017. Neste contexto, o câncer de mama (CM) é o mais incidente em mulheres, atingindo cerca de 28% das brasileiras. A radioterapia constitui em uma modalidade terapêutica amplamente empregada no tratamento de CM em diversos estágios. Porém, radiorresistência, síndrome cutânea da radiação, incidência de novas neoplasias em células saudáveis irradiadas compõem os principais efeitos colaterais dessa prática. Dessa forma, este trabalho buscou investigar o potencial do resveratrol (RV) como radiomodificador do tipo radiossensibilizador em células de CM da linhagem MCF-7. Para isso, as células foram tratadas inicialmente com diferentes doses de RV (0, 10, 30 e 100μM) por 24 horas e então foram expostas à radiação ionizante (RI) (0, 1, 2 e 3 grays). Os resultados mostraram que a combinação de tratamentos mais citotóxica foi 10 μM e 3 grays, sendo essas doses escolhidas para os testes complementares. A análise de morte celular através de citometria de fluxo mostrou que em culturas de 24 horas após a RI a necrose/senescência parece estar relacionada à citoxicidade, além da ativação da via extrínseca da apoptose, fenômeno que ficou claro ao observar a alta atividade das caspases 3 e 8 e baixa na relação bax/bcl-2. Testes envolvendo o metabolismo oxidativo mostraram que RV+RI são eficazes juntos, no sentido de proporcionar alto dano oxidativo ao DNA, proteínas e lipídios celulares, bem como diminuir a atividade das enzimas antioxidantes superóxido dismutase (SOD) e catalase (CAT). A alta expressão de p53, não está envolvida primeiramente na apoptose intrínseca, mas sim no bloqueio da fase S do ciclo celular, que foi observado em culturas de células 72 horas após a RI. Assim, a condição pro-oxidante estabelecida pela combinação dos tratamentos, junto ao alto nível de expressão de p53 permite sugerir que a diminuição expressiva da proliferação celular em culturas de 72 horas parece estar relacionada a parada irreversível de crescimento ligada a necrose/senescência, bem como a ativação da apoptose.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em FarmacologiaUFSMBrasilFarmacologiaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessRadiação ionizanteResveratrolRadioterapiaNeoplasiasRadiossensibilizaçãoIonizing radiationResveratrolRadiotherapyRadiosensitizationCNPQ::CIENCIAS DA SAUDE::FARMACIAAvaliação do efeito radiomodificador do resveratrol sobre células de câncer de mama (MCF-7) irradiadasEvaluation of resveratrol radiomodifier effect on irradiated breast cancer cells (MCF-7)info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisBauermann, Liliane de Freitashttp://lattes.cnpq.br/5849925846135968Fachinetto, Roseleihttp://lattes.cnpq.br/7203076675431306Machado, Michel Mansurhttp://lattes.cnpq.br/7651341120825287http://lattes.cnpq.br/3517758264213389Araldi, Isabel Cristina da Costa400300000005600948e5e71-a7c8-46ad-983f-f52ac6f2ac2183a2ca65-e228-4fa1-a59f-305488f5c947d4a64262-0e7e-45c5-910e-0b0aee907c10fad860ca-fefe-46b6-b0ab-6c96a9bef011reponame:Repositório Institucional Manancial UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDIS_PPGFARMACOLOGIA_2016_ARALDI_ISABEL.pdfDIS_PPGFARMACOLOGIA_2016_ARALDI_ISABEL.pdfDissertação de Mestradoapplication/pdf1908044http://repositorio.ufsm.br/bitstream/1/18149/1/DIS_PPGFARMACOLOGIA_2016_ARALDI_ISABEL.pdf8d2d54ff86ded542aeb6a3a4dcb70214MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Avaliação do efeito radiomodificador do resveratrol sobre células de câncer de mama (MCF-7) irradiadas |
dc.title.alternative.eng.fl_str_mv |
Evaluation of resveratrol radiomodifier effect on irradiated breast cancer cells (MCF-7) |
title |
Avaliação do efeito radiomodificador do resveratrol sobre células de câncer de mama (MCF-7) irradiadas |
spellingShingle |
Avaliação do efeito radiomodificador do resveratrol sobre células de câncer de mama (MCF-7) irradiadas Araldi, Isabel Cristina da Costa Radiação ionizante Resveratrol Radioterapia Neoplasias Radiossensibilização Ionizing radiation Resveratrol Radiotherapy Radiosensitization CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Avaliação do efeito radiomodificador do resveratrol sobre células de câncer de mama (MCF-7) irradiadas |
title_full |
Avaliação do efeito radiomodificador do resveratrol sobre células de câncer de mama (MCF-7) irradiadas |
title_fullStr |
Avaliação do efeito radiomodificador do resveratrol sobre células de câncer de mama (MCF-7) irradiadas |
title_full_unstemmed |
Avaliação do efeito radiomodificador do resveratrol sobre células de câncer de mama (MCF-7) irradiadas |
title_sort |
Avaliação do efeito radiomodificador do resveratrol sobre células de câncer de mama (MCF-7) irradiadas |
author |
Araldi, Isabel Cristina da Costa |
author_facet |
Araldi, Isabel Cristina da Costa |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Bauermann, Liliane de Freitas |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/5849925846135968 |
dc.contributor.referee1.fl_str_mv |
Fachinetto, Roselei |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/7203076675431306 |
dc.contributor.referee2.fl_str_mv |
Machado, Michel Mansur |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/7651341120825287 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/3517758264213389 |
dc.contributor.author.fl_str_mv |
Araldi, Isabel Cristina da Costa |
contributor_str_mv |
Bauermann, Liliane de Freitas Fachinetto, Roselei Machado, Michel Mansur |
dc.subject.por.fl_str_mv |
Radiação ionizante Resveratrol Radioterapia Neoplasias Radiossensibilização |
topic |
Radiação ionizante Resveratrol Radioterapia Neoplasias Radiossensibilização Ionizing radiation Resveratrol Radiotherapy Radiosensitization CNPQ::CIENCIAS DA SAUDE::FARMACIA |
dc.subject.eng.fl_str_mv |
Ionizing radiation Resveratrol Radiotherapy Radiosensitization |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Malignant neoplasias constitute a public health issue, with around 600 thousand new cases of cancer projected to be diagnosed in Brazil between 2016 and 2017. In this context, breast cancer is the most common type in women, reaching around 28% of Brazilian women. Radiation therapy is a therapeutic modality commonly applied in cases of breast cancer in different stages. However, radioresistance, cutaneous radiation syndrome and the occurrence of new neoplasias in healthy cells are the main side effects of this practice. Therefore, the aim of this work was to assess the potential of resveratrol (RV) as a radiosensitizer radiomodifier on breast cancer cells of the lineage MCF-7. For this end, cells were initially treated with different RV doses (0, 10, 30 and 100μM) for 24 hours and then exposed to ionizing radiation (IR) (0, 1, 2 e 3 grays). The results show that the most cytotoxic treatment combination was 10μM and 3 grays, which were the doses chosen for the additional tests. Cellular death assessment through flow cytometry showed that, in 24 hours cell cultures after IR, necrosis/senescence seem to be related to cytotoxicity, besides the activation of extrinsic apoptosis. This phenomenon was clear when the high activity of caspases 3 and 8, and the low bax/bcl-2 ratio were observed. Tests involving oxidative metabolism show that RV and IR are effective together, causing great oxidative damage in DNA, proteins and cellular lipids, as well as diminishing the activity of the antioxidative enzymes dismutase (SOD) and catalase (CAT). The high expression of p53 indicates not to be primarily related to intrinsic apoptosis, but to be indeed related to the interruption of cell cycle in the S phase, which was observed in 72 hours cellular cultures after IR. Thus, the pro-oxidative condition established by the treatment combination, together with the high level of the p53 expression, allow us to suggest that the significant decrease of cellular proliferation in 72 hours cultures seems to be related to the irreversible growth interruption linked to necrosis/senescence, as well as apoptosis activation. |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016-11-28 |
dc.date.accessioned.fl_str_mv |
2019-09-05T18:12:12Z |
dc.date.available.fl_str_mv |
2019-09-05T18:12:12Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/masterThesis |
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masterThesis |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/18149 |
url |
http://repositorio.ufsm.br/handle/1/18149 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
400300000005 |
dc.relation.confidence.fl_str_mv |
600 |
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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.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Farmacologia |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Farmacologia |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional Manancial UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
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