Efeitos antitumorais e antimetastáticos de novos complexos de rutênio em células de câncer de mama
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFSCAR |
Texto Completo: | https://repositorio.ufscar.br/handle/ufscar/7961 |
Resumo: | Brazil and the world are passing through demographic changes as consequences of population urbanization, industrialization and advances in science and technology. This process, associated with the transformation of society's quality of life has brought a significant change in the morbidity and mortality profile reducing the occurrence of infectious diseases and increasing incidence of chronic degenerative diseases, like cancer. Cancer is a term used for diseases in which abnormal cells divide without control, and are able to spread and invade other tissues through blood and lymphatic systems. Breast cancer is the second most common cancer in the world and can be considered a cancer with a good prognosis if diagnosed early and treated timely. Treatment of breast cancer has as main objectives to increase survival and improve the quality of life of women. Surgery and radiotherapy are responsible for local control of breast cancer; on the other hand, systemic treatment is made by hormone therapy and chemotherapy. Drugs used in chemotherapy cause resistance and damage to DNA, not only of tumor cells, but also of normal cells. Rosenberg and colleagues in 1964, were responsible for the discovery of antitumor drug to base metals, cisplatin, an effective complex and remains widely used in therapies against various types of tumors, however, despite its effectiveness, also has several side effects. With the limitations of cisplatin, new research has been developed with ruthenium complexes. Ruthenium has some unique properties that can justify their antitumor potential, among them the ability to mimic the iron in connection to many biomolecules, including transferrin and albumin. Therefore, the aim of this study was to evaluate the effect of four new ruthenium complexes with bipyridine and biphophine ligands: (1) [Ru(SO4)(dppb)(bipy)], (2) [Ru(CO3)(dppb)(bipy)], (3) [Ru(C2O4)(dppb)(bipy)] e (4) [Ru(CH3CO2)(dppb)(bipy)]PF6 on the proliferation of breast tumor cells, MDA-MB-231 and MCF-7, and a non-tumor cell line MCF-10A. The results demonstrated that the compound (4) was more efficient inhibiting proliferation of triple negative breast cancer cells MDA-MB- 231, compared with the non-tumor cell line MCF-10A which was more resistant to the complex. Futhermore, the complex (4) was able to reduce the number and size of colonies, to act in the metastatic cascade inhibiting the adhesion, migration and invasion. The complex (4) also inhibited the secretion of MMP9 and induced apoptosis by increasing the expression of pro-apoptotic genes such as Bax and Caspase-3 and decreasing anti-apoptotic genes Bcl-2 in triple negative breast cancer cells, MDA-MB-231. These results show that the complex (4) has potential antitumor and antimetastatic to breast tumor cells; it might be a good alternative drug for the treatment of cancer. |
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Popolin, Cecília PatriciaCominetti, Márcia Reginahttp://lattes.cnpq.br/3725318894555272http://lattes.cnpq.br/5598104335028847aec6d7c9-67ca-48ff-8420-67a73c25d83b2016-10-20T16:11:56Z2016-10-20T16:11:56Z2016-04-29POPOLIN, Cecília Patricia. Efeitos antitumorais e antimetastáticos de novos complexos de rutênio em células de câncer de mama. 2016. Dissertação (Mestrado em Ciências Fisiológicas) – Universidade Federal de São Carlos, São Carlos, 2016. Disponível em: https://repositorio.ufscar.br/handle/ufscar/7961.https://repositorio.ufscar.br/handle/ufscar/7961Brazil and the world are passing through demographic changes as consequences of population urbanization, industrialization and advances in science and technology. This process, associated with the transformation of society's quality of life has brought a significant change in the morbidity and mortality profile reducing the occurrence of infectious diseases and increasing incidence of chronic degenerative diseases, like cancer. Cancer is a term used for diseases in which abnormal cells divide without control, and are able to spread and invade other tissues through blood and lymphatic systems. Breast cancer is the second most common cancer in the world and can be considered a cancer with a good prognosis if diagnosed early and treated timely. Treatment of breast cancer has as main objectives to increase survival and improve the quality of life of women. Surgery and radiotherapy are responsible for local control of breast cancer; on the other hand, systemic treatment is made by hormone therapy and chemotherapy. Drugs used in chemotherapy cause resistance and damage to DNA, not only of tumor cells, but also of normal cells. Rosenberg and colleagues in 1964, were responsible for the discovery of antitumor drug to base metals, cisplatin, an effective complex and remains widely used in therapies against various types of tumors, however, despite its effectiveness, also has several side effects. With the limitations of cisplatin, new research has been developed with ruthenium complexes. Ruthenium has some unique properties that can justify their antitumor potential, among them the ability to mimic the iron in connection to many biomolecules, including transferrin and albumin. Therefore, the aim of this study was to evaluate the effect of four new ruthenium complexes with bipyridine and biphophine ligands: (1) [Ru(SO4)(dppb)(bipy)], (2) [Ru(CO3)(dppb)(bipy)], (3) [Ru(C2O4)(dppb)(bipy)] e (4) [Ru(CH3CO2)(dppb)(bipy)]PF6 on the proliferation of breast tumor cells, MDA-MB-231 and MCF-7, and a non-tumor cell line MCF-10A. The results demonstrated that the compound (4) was more efficient inhibiting proliferation of triple negative breast cancer cells MDA-MB- 231, compared with the non-tumor cell line MCF-10A which was more resistant to the complex. Futhermore, the complex (4) was able to reduce the number and size of colonies, to act in the metastatic cascade inhibiting the adhesion, migration and invasion. The complex (4) also inhibited the secretion of MMP9 and induced apoptosis by increasing the expression of pro-apoptotic genes such as Bax and Caspase-3 and decreasing anti-apoptotic genes Bcl-2 in triple negative breast cancer cells, MDA-MB-231. These results show that the complex (4) has potential antitumor and antimetastatic to breast tumor cells; it might be a good alternative drug for the treatment of cancer.As mudanças demográficas que o Brasil e o mundo vêm sofrendo são consequências do processo de urbanização populacional, da industrialização e dos avanços da ciência e da tecnologia. Esse processo, associado à transformação na qualidade de vida da sociedade trouxe uma alteração importante no perfil de morbimortalidade diminuindo a ocorrência das doenças infectocontagiosas e aumentando a incidência das doenças crônico-degenerativas, como o câncer. O câncer é um termo utilizado para doenças em que células anormais se dividem sem controle e são capazes de se espalhar e invadir outros tecidos através dos sistemas sanguíneo e linfático. O câncer de mama é o segundo tipo de câncer mais comum no mundo e pode ser considerado um câncer com bom prognóstico se diagnosticado precocemente e tratado oportunamente. O tratamento do câncer de mama tem como objetivos principais aumentar a sobrevida e melhorar a qualidade de vida da mulher. A cirurgia e a radioterapia respondem pelo controle local do câncer de mama, já o tratamento sistêmico é feito por terapia hormonal ou quimioterapia. Os fármacos utilizados na quimioterapia causam danos ao DNA, tanto das células tumorais, como também das células normais e ainda as células tumorais podem se tornar resistentes a esses fármacos. Rosenberg e colaboradores em 1964 foram responsáveis pela descoberta do fármaco antitumoral a base de metais, a cisplatina, um complexo eficaz e ainda muito utilizada em terapias contra vários tipos de tumores, porém, apesar de sua eficácia, apresenta também diversos efeitos colaterais. Com as limitações da cisplatina, novas pesquisas vêm sendo desenvolvidas com complexos de rutênio. O rutênio possui algumas propriedades únicas que podem justificar seu potencial antitumoral, dentre elas, a capacidade de imitar o ferro na ligação a muitas biomoléculas, incluindo a transferrina e albumina. Portanto, o objetivo do presente trabalho foi avaliar o efeito de quatro novos complexos de rutênio com ligantes bipiridina e bifosfina: (1) [Ru(SO4)(dppb)(bipy)], (2) [Ru(CO3)(dppb)(bipy)], (3) [Ru(C2O4)(dppb)(bipy)] e (4) [Ru(CH3CO2)(dppb)(bipy)]PF6 sobre a proliferação de células tumorais de mama, da linhagem MDA-MB-231 e MCF-7, e da linhagem não-tumoral de mama, MCF- 10A. Os resultados demonstraram que o complexo (4) foi o mais eficaz em inibir a proliferação das células tumorais de mama triplo negativas, da linhagem MDA-MB-231, em comparação com a linhagem não tumoral de mama MCF-10A que se mostrou mais resistente ao complexo. Ainda, o complexo (4) foi capaz diminuir o número e tamanho de colônias, de modificar o citoesqueleto e de atuar na cascata metastática inibindo a adesão, migração e invasão, das células tumorais de mama, da linhagem MDA-MB-231. O complexo (4) inibiu também a secreção de MMP9 e induziu a apoptose aumentando a expressão de genes pró-apoptóticos como Bax e Caspase-3 e diminuindo a expressão genes anti-apoptóticos Bcl-2, nas células tumorais de mama triplo negativas, da linhagem MDA-MB-231. Esses resultados mostram que o complexo (4) possui potencial antitumoral e antimetastático para células tumorais de mama, podendo ser uma nova alternativa de fármaco para o tratamento do câncer.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)porUniversidade Federal de São CarlosCâmpus São CarlosPrograma Interinstitucional de Pós-Graduação em Ciências Fisiológicas - PIPGCFUFSCarCâncerComplexos de rutênioCâncer de mamaMetástaseApoptoseRuthenium complexesBreast cancerMetastasisApoptosisCIENCIAS BIOLOGICAS::FISIOLOGIAEfeitos antitumorais e antimetastáticos de novos complexos de rutênio em células de câncer de mamainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisOnline6006006fbc146e-b953-4aee-ae8e-f34e0b675891info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINALDissCPPea.pdfDissCPPea.pdfapplication/pdf2905198https://repositorio.ufscar.br/bitstream/ufscar/7961/1/DissCPPea.pdf275d7295d9622b8450ea88c731d212ebMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81957https://repositorio.ufscar.br/bitstream/ufscar/7961/2/license.txtae0398b6f8b235e40ad82cba6c50031dMD52TEXTDissCPPea.pdf.txtDissCPPea.pdf.txtExtracted texttext/plain119618https://repositorio.ufscar.br/bitstream/ufscar/7961/3/DissCPPea.pdf.txt7cdff69273ed595031ed40f6e9ec2216MD53THUMBNAILDissCPPea.pdf.jpgDissCPPea.pdf.jpgIM Thumbnailimage/jpeg6676https://repositorio.ufscar.br/bitstream/ufscar/7961/4/DissCPPea.pdf.jpge6b0a58e3e5ef27d42dea49a294dae08MD54ufscar/79612023-09-18 18:30:56.719oai:repositorio.ufscar.br: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Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222023-09-18T18:30:56Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false |
dc.title.por.fl_str_mv |
Efeitos antitumorais e antimetastáticos de novos complexos de rutênio em células de câncer de mama |
title |
Efeitos antitumorais e antimetastáticos de novos complexos de rutênio em células de câncer de mama |
spellingShingle |
Efeitos antitumorais e antimetastáticos de novos complexos de rutênio em células de câncer de mama Popolin, Cecília Patricia Câncer Complexos de rutênio Câncer de mama Metástase Apoptose Ruthenium complexes Breast cancer Metastasis Apoptosis CIENCIAS BIOLOGICAS::FISIOLOGIA |
title_short |
Efeitos antitumorais e antimetastáticos de novos complexos de rutênio em células de câncer de mama |
title_full |
Efeitos antitumorais e antimetastáticos de novos complexos de rutênio em células de câncer de mama |
title_fullStr |
Efeitos antitumorais e antimetastáticos de novos complexos de rutênio em células de câncer de mama |
title_full_unstemmed |
Efeitos antitumorais e antimetastáticos de novos complexos de rutênio em células de câncer de mama |
title_sort |
Efeitos antitumorais e antimetastáticos de novos complexos de rutênio em células de câncer de mama |
author |
Popolin, Cecília Patricia |
author_facet |
Popolin, Cecília Patricia |
author_role |
author |
dc.contributor.authorlattes.por.fl_str_mv |
http://lattes.cnpq.br/5598104335028847 |
dc.contributor.author.fl_str_mv |
Popolin, Cecília Patricia |
dc.contributor.advisor1.fl_str_mv |
Cominetti, Márcia Regina |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/3725318894555272 |
dc.contributor.authorID.fl_str_mv |
aec6d7c9-67ca-48ff-8420-67a73c25d83b |
contributor_str_mv |
Cominetti, Márcia Regina |
dc.subject.por.fl_str_mv |
Câncer Complexos de rutênio Câncer de mama Metástase Apoptose |
topic |
Câncer Complexos de rutênio Câncer de mama Metástase Apoptose Ruthenium complexes Breast cancer Metastasis Apoptosis CIENCIAS BIOLOGICAS::FISIOLOGIA |
dc.subject.eng.fl_str_mv |
Ruthenium complexes Breast cancer Metastasis Apoptosis |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS::FISIOLOGIA |
description |
Brazil and the world are passing through demographic changes as consequences of population urbanization, industrialization and advances in science and technology. This process, associated with the transformation of society's quality of life has brought a significant change in the morbidity and mortality profile reducing the occurrence of infectious diseases and increasing incidence of chronic degenerative diseases, like cancer. Cancer is a term used for diseases in which abnormal cells divide without control, and are able to spread and invade other tissues through blood and lymphatic systems. Breast cancer is the second most common cancer in the world and can be considered a cancer with a good prognosis if diagnosed early and treated timely. Treatment of breast cancer has as main objectives to increase survival and improve the quality of life of women. Surgery and radiotherapy are responsible for local control of breast cancer; on the other hand, systemic treatment is made by hormone therapy and chemotherapy. Drugs used in chemotherapy cause resistance and damage to DNA, not only of tumor cells, but also of normal cells. Rosenberg and colleagues in 1964, were responsible for the discovery of antitumor drug to base metals, cisplatin, an effective complex and remains widely used in therapies against various types of tumors, however, despite its effectiveness, also has several side effects. With the limitations of cisplatin, new research has been developed with ruthenium complexes. Ruthenium has some unique properties that can justify their antitumor potential, among them the ability to mimic the iron in connection to many biomolecules, including transferrin and albumin. Therefore, the aim of this study was to evaluate the effect of four new ruthenium complexes with bipyridine and biphophine ligands: (1) [Ru(SO4)(dppb)(bipy)], (2) [Ru(CO3)(dppb)(bipy)], (3) [Ru(C2O4)(dppb)(bipy)] e (4) [Ru(CH3CO2)(dppb)(bipy)]PF6 on the proliferation of breast tumor cells, MDA-MB-231 and MCF-7, and a non-tumor cell line MCF-10A. The results demonstrated that the compound (4) was more efficient inhibiting proliferation of triple negative breast cancer cells MDA-MB- 231, compared with the non-tumor cell line MCF-10A which was more resistant to the complex. Futhermore, the complex (4) was able to reduce the number and size of colonies, to act in the metastatic cascade inhibiting the adhesion, migration and invasion. The complex (4) also inhibited the secretion of MMP9 and induced apoptosis by increasing the expression of pro-apoptotic genes such as Bax and Caspase-3 and decreasing anti-apoptotic genes Bcl-2 in triple negative breast cancer cells, MDA-MB-231. These results show that the complex (4) has potential antitumor and antimetastatic to breast tumor cells; it might be a good alternative drug for the treatment of cancer. |
publishDate |
2016 |
dc.date.accessioned.fl_str_mv |
2016-10-20T16:11:56Z |
dc.date.available.fl_str_mv |
2016-10-20T16:11:56Z |
dc.date.issued.fl_str_mv |
2016-04-29 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/masterThesis |
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dc.identifier.citation.fl_str_mv |
POPOLIN, Cecília Patricia. Efeitos antitumorais e antimetastáticos de novos complexos de rutênio em células de câncer de mama. 2016. Dissertação (Mestrado em Ciências Fisiológicas) – Universidade Federal de São Carlos, São Carlos, 2016. Disponível em: https://repositorio.ufscar.br/handle/ufscar/7961. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufscar.br/handle/ufscar/7961 |
identifier_str_mv |
POPOLIN, Cecília Patricia. Efeitos antitumorais e antimetastáticos de novos complexos de rutênio em células de câncer de mama. 2016. Dissertação (Mestrado em Ciências Fisiológicas) – Universidade Federal de São Carlos, São Carlos, 2016. Disponível em: https://repositorio.ufscar.br/handle/ufscar/7961. |
url |
https://repositorio.ufscar.br/handle/ufscar/7961 |
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openAccess |
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Universidade Federal de São Carlos Câmpus São Carlos |
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Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas - PIPGCF |
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UFSCar |
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Universidade Federal de São Carlos Câmpus São Carlos |
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