Efeito citotóxico e pró-apoptótico do composto [6]-Shogaol contra células de câncer de bexiga (MB49), in vitro
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFSCAR |
Texto Completo: | https://repositorio.ufscar.br/handle/ufscar/14568 |
Resumo: | Bladder cancer is considered one of the most aggressive malignancies due to its profile of recurrence and progression, and even with the improvement in methods of diagnosis and treatment, the mortality rate has not shown a declining trend in recent decades worldwide. In this perspective, the search and development of more effective and safer therapeutic alternatives is necessary. Phytochemicals are excellent sources of active ingredients with therapeutic potential, which have been used for centuries for therapeutic and culinary purposes. [6]-Shogaol is a phenolic compound extracted from the rhizome of ginger (Zingiber officinale Roscoe) that has shown antiproliferative and anti-tumor effects in a wide variety of cancer models, both in vitro and in vivo. However, there are no records of studies reporting an antitumor effect in cell models of bladder cancer. Thus, this study aimed to investigate the in vitro cytotoxic and pro-apoptotic potential of [6]-Shogaol against murine bladder cancer urothelial cells (MB49), in relation to non-tumor murine fibroblasts (L929). Through the in vitro study, the cytotoxic and pro-apoptotic effect was evaluated, through the analysis of the reduction of the metabolic activity, observation of morphological alterations associated with cellular damage, identification of alterations in the process of colony formation, evaluation of the level of reactive species of intracellular oxygen, evaluation of alterations in the nuclear structure, identification of apoptosis events and assessment of anti-migratory potential. Based on the results, it was shown that [6]-Shogaol was able to induce cytotoxic effects that compromised cell viability, exhibiting an inhibitory concentration of 50% of cells (IC50) of 135,5 µM for tumor cells MB49 and 205,3 µM for L929 non tumor fibroblasts, in addition to inhibiting and altering the proliferative processes of colony formation, showed pro-apoptotic activity identified by the observation of apoptotic phenotypes, mediated by nuclear fragmentation. In summary, our study suggests that [6]-Shogaol causes cytotoxic damage that compromises the viability of MB49 murine bladder tumor cells in a concentration-dependent manner. It can be suggested that [6]-Shogaol is promising for delineation in more in-depth studies to understand its antitumor properties, as it is a strong phytotherapeutic candidate in the treatment of bladder cancer. |
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Nina, Diana Gabriela NinaAnibal, Fernanda de Freitashttp://lattes.cnpq.br/4918261968772806http://lattes.cnpq.br/468787769384058653822785-086e-4fd6-abcb-7c8087368f2a2021-07-10T10:32:13Z2021-07-10T10:32:13Z2021-05-24NINA, Diana Gabriela Nina. Efeito citotóxico e pró-apoptótico do composto [6]-Shogaol contra células de câncer de bexiga (MB49), in vitro. 2021. Dissertação (Mestrado em Genética Evolutiva e Biologia Molecular) – Universidade Federal de São Carlos, São Carlos, 2021. Disponível em: https://repositorio.ufscar.br/handle/ufscar/14568.https://repositorio.ufscar.br/handle/ufscar/14568Bladder cancer is considered one of the most aggressive malignancies due to its profile of recurrence and progression, and even with the improvement in methods of diagnosis and treatment, the mortality rate has not shown a declining trend in recent decades worldwide. In this perspective, the search and development of more effective and safer therapeutic alternatives is necessary. Phytochemicals are excellent sources of active ingredients with therapeutic potential, which have been used for centuries for therapeutic and culinary purposes. [6]-Shogaol is a phenolic compound extracted from the rhizome of ginger (Zingiber officinale Roscoe) that has shown antiproliferative and anti-tumor effects in a wide variety of cancer models, both in vitro and in vivo. However, there are no records of studies reporting an antitumor effect in cell models of bladder cancer. Thus, this study aimed to investigate the in vitro cytotoxic and pro-apoptotic potential of [6]-Shogaol against murine bladder cancer urothelial cells (MB49), in relation to non-tumor murine fibroblasts (L929). Through the in vitro study, the cytotoxic and pro-apoptotic effect was evaluated, through the analysis of the reduction of the metabolic activity, observation of morphological alterations associated with cellular damage, identification of alterations in the process of colony formation, evaluation of the level of reactive species of intracellular oxygen, evaluation of alterations in the nuclear structure, identification of apoptosis events and assessment of anti-migratory potential. Based on the results, it was shown that [6]-Shogaol was able to induce cytotoxic effects that compromised cell viability, exhibiting an inhibitory concentration of 50% of cells (IC50) of 135,5 µM for tumor cells MB49 and 205,3 µM for L929 non tumor fibroblasts, in addition to inhibiting and altering the proliferative processes of colony formation, showed pro-apoptotic activity identified by the observation of apoptotic phenotypes, mediated by nuclear fragmentation. In summary, our study suggests that [6]-Shogaol causes cytotoxic damage that compromises the viability of MB49 murine bladder tumor cells in a concentration-dependent manner. It can be suggested that [6]-Shogaol is promising for delineation in more in-depth studies to understand its antitumor properties, as it is a strong phytotherapeutic candidate in the treatment of bladder cancer.O câncer de bexiga é considerado uma das neoplasias malignas mais agressivas devido a seu perfil de recorrência e progressão, e mesmo com a melhora nos métodos de diagnóstico e tratamento, a taxa de mortalidade não tem apresentado uma tendência de declínio nas últimas décadas a nível mundial. Nessa perspectiva, a procura e o desenvolvimento de alternativas terapêuticas mais eficazes e seguras é necessário. Os fitoquímicos são excelentes fontes de princípios ativos com potencial terapêutico, que têm sido usados desde há séculos com fins terapêuticos e culinários. O [6]-Shogaol é um composto fenólico extraído do rizoma do gengibre (Zingiber officinale Roscoe) que tem apresentado efeitos antiproliferativos e antitumorais em uma ampla variedade de modelos de cânceres, tanto in vitro, quanto in vivo. No entanto, não se têm registros de estudos que relatem um efeito antitumoral em modelos celulares de câncer de bexiga. Dessa forma, este estudo teve como objetivo investigar o potencial citotóxico e pró-apoptótico in vitro do [6]-Shogaol contra células uroteliais de câncer de bexiga murinas (MB49), em relação a fibroblastos murinos não tumorais (L929). Por meio do estudo in vitro foi avaliado o efeito citotóxico e pró-apoptótico, mediante a análise da redução da atividade metabólica, observação de alterações morfológicas associadas a dano celular, identificação de alterações no processo de formação de colônias, avaliação do nível de espécies reativas de oxigênio intracelular, avaliação de alterações na estrutura nuclear, identificação de eventos de apoptoses e a avaliação do potencial anti-migratório. Com base nos resultados, se evidenciou que [6]-Shogaol foi capaz induzir efeitos citotóxicos que comprometeram a viabilidade celular, exibindo uma concentração inibitória de 50% das células (IC50) de 135,5 µM para as células tumorais MB49 e de 205,3 µM para os fibroblastos não tumorais L929, além de inibir e alterar os processos proliferativos de formação de colônias, apresentou atividade pró-apoptótica identificada pela observação de fenótipos apoptóticos, mediada pela fragmentação nuclear. Em suma, nosso estudo sugere que [6]-Shogaol provoca danos citotóxicos que comprometem a viabilidade das células tumorais murinas de bexiga MB49, de maneira dependente da concentração. Pode-se sugerir que [6]-Shogaol é promissor para delineamento em estudos mais aprofundados para compreender suas propriedades antitumorais, por ser um forte candidato fitoterápico no tratamento para o câncer de bexiga.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)CAPES: 88882.426730/2019-01porUniversidade Federal de São CarlosCâmpus São CarlosPrograma de Pós-Graduação em Genética Evolutiva e Biologia Molecular - PPGGEvUFSCarAttribution-NonCommercial-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nc-nd/3.0/br/info:eu-repo/semantics/openAccessCâncer de bexigaCitotóxicoFitoterápicoPró-apoptótico [6]-ShogaolBladder cancerCytotoxicPhytotherapicPro-apoptotic [6]-ShogaolIC50CIENCIAS BIOLOGICAS::BIOQUIMICA::BIOLOGIA MOLECULARCIENCIAS BIOLOGICAS::BIOQUIMICAEfeito citotóxico e pró-apoptótico do composto [6]-Shogaol contra células de câncer de bexiga (MB49), in vitrocytotoxic and pro-apoptotic effect of [6]-Shogaol compound against bladder cancer cells (MB49), in vitroinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis600600d0b619ca-16cf-40f9-9e9b-1792083fa39freponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINALDissertação Diana Gabriela Nina .pdfDissertação Diana Gabriela Nina .pdfapplication/pdf6033696https://repositorio.ufscar.br/bitstream/ufscar/14568/1/Disserta%c3%a7%c3%a3o%20Diana%20Gabriela%20Nina%20.pdf76f07d8586c89c069c91857ba8bbcc7cMD51carta-comprovante DIANA NINA.pdfcarta-comprovante DIANA NINA.pdfapplication/pdf88323https://repositorio.ufscar.br/bitstream/ufscar/14568/4/carta-comprovante%20DIANA%20NINA.pdf9250eaf34d4c7aaa9152f2331ea6506dMD54CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8811https://repositorio.ufscar.br/bitstream/ufscar/14568/5/license_rdfe39d27027a6cc9cb039ad269a5db8e34MD55TEXTDissertação Diana Gabriela Nina .pdf.txtDissertação Diana Gabriela Nina .pdf.txtExtracted texttext/plain189957https://repositorio.ufscar.br/bitstream/ufscar/14568/6/Disserta%c3%a7%c3%a3o%20Diana%20Gabriela%20Nina%20.pdf.txtedb8a4a0ecd2c345c8b44c0aea4e2e50MD56carta-comprovante DIANA NINA.pdf.txtcarta-comprovante DIANA NINA.pdf.txtExtracted texttext/plain1208https://repositorio.ufscar.br/bitstream/ufscar/14568/8/carta-comprovante%20DIANA%20NINA.pdf.txt8496f26ff90844e093449c82b79a7db7MD58THUMBNAILDissertação Diana Gabriela Nina .pdf.jpgDissertação Diana Gabriela Nina .pdf.jpgIM Thumbnailimage/jpeg7219https://repositorio.ufscar.br/bitstream/ufscar/14568/7/Disserta%c3%a7%c3%a3o%20Diana%20Gabriela%20Nina%20.pdf.jpg7fc9371c4f8890da0dce896e31e63f89MD57carta-comprovante DIANA NINA.pdf.jpgcarta-comprovante DIANA NINA.pdf.jpgIM Thumbnailimage/jpeg6280https://repositorio.ufscar.br/bitstream/ufscar/14568/9/carta-comprovante%20DIANA%20NINA.pdf.jpgab159c7f5795c7807b52644a0a46f93eMD59ufscar/145682023-09-18 18:32:13.109oai:repositorio.ufscar.br:ufscar/14568Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222023-09-18T18:32:13Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false |
dc.title.por.fl_str_mv |
Efeito citotóxico e pró-apoptótico do composto [6]-Shogaol contra células de câncer de bexiga (MB49), in vitro |
dc.title.alternative.eng.fl_str_mv |
cytotoxic and pro-apoptotic effect of [6]-Shogaol compound against bladder cancer cells (MB49), in vitro |
title |
Efeito citotóxico e pró-apoptótico do composto [6]-Shogaol contra células de câncer de bexiga (MB49), in vitro |
spellingShingle |
Efeito citotóxico e pró-apoptótico do composto [6]-Shogaol contra células de câncer de bexiga (MB49), in vitro Nina, Diana Gabriela Nina Câncer de bexiga Citotóxico Fitoterápico Pró-apoptótico [6]-Shogaol Bladder cancer Cytotoxic Phytotherapic Pro-apoptotic [6]-Shogaol IC50 CIENCIAS BIOLOGICAS::BIOQUIMICA::BIOLOGIA MOLECULAR CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Efeito citotóxico e pró-apoptótico do composto [6]-Shogaol contra células de câncer de bexiga (MB49), in vitro |
title_full |
Efeito citotóxico e pró-apoptótico do composto [6]-Shogaol contra células de câncer de bexiga (MB49), in vitro |
title_fullStr |
Efeito citotóxico e pró-apoptótico do composto [6]-Shogaol contra células de câncer de bexiga (MB49), in vitro |
title_full_unstemmed |
Efeito citotóxico e pró-apoptótico do composto [6]-Shogaol contra células de câncer de bexiga (MB49), in vitro |
title_sort |
Efeito citotóxico e pró-apoptótico do composto [6]-Shogaol contra células de câncer de bexiga (MB49), in vitro |
author |
Nina, Diana Gabriela Nina |
author_facet |
Nina, Diana Gabriela Nina |
author_role |
author |
dc.contributor.authorlattes.por.fl_str_mv |
http://lattes.cnpq.br/4687877693840586 |
dc.contributor.author.fl_str_mv |
Nina, Diana Gabriela Nina |
dc.contributor.advisor1.fl_str_mv |
Anibal, Fernanda de Freitas |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/4918261968772806 |
dc.contributor.authorID.fl_str_mv |
53822785-086e-4fd6-abcb-7c8087368f2a |
contributor_str_mv |
Anibal, Fernanda de Freitas |
dc.subject.por.fl_str_mv |
Câncer de bexiga Citotóxico Fitoterápico Pró-apoptótico [6]-Shogaol |
topic |
Câncer de bexiga Citotóxico Fitoterápico Pró-apoptótico [6]-Shogaol Bladder cancer Cytotoxic Phytotherapic Pro-apoptotic [6]-Shogaol IC50 CIENCIAS BIOLOGICAS::BIOQUIMICA::BIOLOGIA MOLECULAR CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Bladder cancer Cytotoxic Phytotherapic Pro-apoptotic [6]-Shogaol IC50 |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS::BIOQUIMICA::BIOLOGIA MOLECULAR CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Bladder cancer is considered one of the most aggressive malignancies due to its profile of recurrence and progression, and even with the improvement in methods of diagnosis and treatment, the mortality rate has not shown a declining trend in recent decades worldwide. In this perspective, the search and development of more effective and safer therapeutic alternatives is necessary. Phytochemicals are excellent sources of active ingredients with therapeutic potential, which have been used for centuries for therapeutic and culinary purposes. [6]-Shogaol is a phenolic compound extracted from the rhizome of ginger (Zingiber officinale Roscoe) that has shown antiproliferative and anti-tumor effects in a wide variety of cancer models, both in vitro and in vivo. However, there are no records of studies reporting an antitumor effect in cell models of bladder cancer. Thus, this study aimed to investigate the in vitro cytotoxic and pro-apoptotic potential of [6]-Shogaol against murine bladder cancer urothelial cells (MB49), in relation to non-tumor murine fibroblasts (L929). Through the in vitro study, the cytotoxic and pro-apoptotic effect was evaluated, through the analysis of the reduction of the metabolic activity, observation of morphological alterations associated with cellular damage, identification of alterations in the process of colony formation, evaluation of the level of reactive species of intracellular oxygen, evaluation of alterations in the nuclear structure, identification of apoptosis events and assessment of anti-migratory potential. Based on the results, it was shown that [6]-Shogaol was able to induce cytotoxic effects that compromised cell viability, exhibiting an inhibitory concentration of 50% of cells (IC50) of 135,5 µM for tumor cells MB49 and 205,3 µM for L929 non tumor fibroblasts, in addition to inhibiting and altering the proliferative processes of colony formation, showed pro-apoptotic activity identified by the observation of apoptotic phenotypes, mediated by nuclear fragmentation. In summary, our study suggests that [6]-Shogaol causes cytotoxic damage that compromises the viability of MB49 murine bladder tumor cells in a concentration-dependent manner. It can be suggested that [6]-Shogaol is promising for delineation in more in-depth studies to understand its antitumor properties, as it is a strong phytotherapeutic candidate in the treatment of bladder cancer. |
publishDate |
2021 |
dc.date.accessioned.fl_str_mv |
2021-07-10T10:32:13Z |
dc.date.available.fl_str_mv |
2021-07-10T10:32:13Z |
dc.date.issued.fl_str_mv |
2021-05-24 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/masterThesis |
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masterThesis |
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dc.identifier.citation.fl_str_mv |
NINA, Diana Gabriela Nina. Efeito citotóxico e pró-apoptótico do composto [6]-Shogaol contra células de câncer de bexiga (MB49), in vitro. 2021. Dissertação (Mestrado em Genética Evolutiva e Biologia Molecular) – Universidade Federal de São Carlos, São Carlos, 2021. Disponível em: https://repositorio.ufscar.br/handle/ufscar/14568. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufscar.br/handle/ufscar/14568 |
identifier_str_mv |
NINA, Diana Gabriela Nina. Efeito citotóxico e pró-apoptótico do composto [6]-Shogaol contra células de câncer de bexiga (MB49), in vitro. 2021. Dissertação (Mestrado em Genética Evolutiva e Biologia Molecular) – Universidade Federal de São Carlos, São Carlos, 2021. Disponível em: https://repositorio.ufscar.br/handle/ufscar/14568. |
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https://repositorio.ufscar.br/handle/ufscar/14568 |
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Attribution-NonCommercial-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nc-nd/3.0/br/ info:eu-repo/semantics/openAccess |
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Universidade Federal de São Carlos Câmpus São Carlos |
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Programa de Pós-Graduação em Genética Evolutiva e Biologia Molecular - PPGGEv |
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UFSCar |
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Universidade Federal de São Carlos Câmpus São Carlos |
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