COMPOSTOS CITOTÓXICOS DA BIODIVERSIDADE BRASILEIRA COMBINADOS À DOXORUBICINA NO TRATAMENTO DE CÂNCER DE MAMA EM MODELOS DE CULTURA CELULAR 2D E 3D

Detalhes bibliográficos
Autor(a) principal: MARIAH OJEDA
Data de Publicação: 2021
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFMS
Texto Completo: https://repositorio.ufms.br/handle/123456789/3855
Resumo: Introduction: Breast cancer affects millions of women worldwide and is the second type of cancer that most affects women (behind non-melanoma skin cancer). It is estimated that more than 600 thousand new cases of cancer will occur annually between 2020 until 2022. The use of polytherapy is common in the treatment of cancer and has the advantage of greater efficacy in the different subpopulations of the tumor, in addition to avoiding drug resistance. The association of standardized chemotherapy with natural products such as isoflavonoids and terpenes is of great importance, considering the biological potential in their derivatives. Objectives: To evaluate the action at the cellular level of cytotoxic compounds from Brazilian biodiversity (black propolis and C. Mellifluum) combined with chemotherapeutic agents doxorubicin in the Methodology and Results: The results of cytotoxicity in 2D model in the neoplastic lineage MCF-7 show an IC50 of 4.089µg/mL for SBP (isoflavonoid from black propolis) and 3.895µg/mL for SCM (triterpene originated from C. Mellifluum). The cytotoxicity of these compounds was evaluated after mimicking hepatic metabolism in vitro, observing that there was no inactivation of the substance and the cytotoxic activity was preserved. Both compounds were able to inhibit cell migration in potentially metastatic language, in addition to inhibiting the formation of colonies of neoplastic cells when associated with doxorubicin. The samples were able to stimulate cell membrane damage represented by the elevation of TBARS levels and the response of antioxidant defenses. In the investigation carried out in 3D model, it is noticed that the SCM compound when associated with doxorubicin can penetrate more into the formed spheroid. SBP and SCM were able to promote damage to the cell membrane and interrupt the cell cycle in the G1 phase, before the cell entered the S phase related to the synthesis of genetic material. Conclusions: The data found from the evaluation of the isolated compounds corroborate with that described in the literature regarding cytotoxic activity. It is necessary to advance the studies to better understand the mechanism of inhibition of cell migration and how the compounds act in the cell cycle. Keywords: Combretum mellifluum, black propolis, cytotoxicity, spheroids, cell migration, cell culture
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spelling 2021-07-26T19:38:26Z2021-09-30T19:56:34Z2021https://repositorio.ufms.br/handle/123456789/3855Introduction: Breast cancer affects millions of women worldwide and is the second type of cancer that most affects women (behind non-melanoma skin cancer). It is estimated that more than 600 thousand new cases of cancer will occur annually between 2020 until 2022. The use of polytherapy is common in the treatment of cancer and has the advantage of greater efficacy in the different subpopulations of the tumor, in addition to avoiding drug resistance. The association of standardized chemotherapy with natural products such as isoflavonoids and terpenes is of great importance, considering the biological potential in their derivatives. Objectives: To evaluate the action at the cellular level of cytotoxic compounds from Brazilian biodiversity (black propolis and C. Mellifluum) combined with chemotherapeutic agents doxorubicin in the Methodology and Results: The results of cytotoxicity in 2D model in the neoplastic lineage MCF-7 show an IC50 of 4.089µg/mL for SBP (isoflavonoid from black propolis) and 3.895µg/mL for SCM (triterpene originated from C. Mellifluum). The cytotoxicity of these compounds was evaluated after mimicking hepatic metabolism in vitro, observing that there was no inactivation of the substance and the cytotoxic activity was preserved. Both compounds were able to inhibit cell migration in potentially metastatic language, in addition to inhibiting the formation of colonies of neoplastic cells when associated with doxorubicin. The samples were able to stimulate cell membrane damage represented by the elevation of TBARS levels and the response of antioxidant defenses. In the investigation carried out in 3D model, it is noticed that the SCM compound when associated with doxorubicin can penetrate more into the formed spheroid. SBP and SCM were able to promote damage to the cell membrane and interrupt the cell cycle in the G1 phase, before the cell entered the S phase related to the synthesis of genetic material. Conclusions: The data found from the evaluation of the isolated compounds corroborate with that described in the literature regarding cytotoxic activity. It is necessary to advance the studies to better understand the mechanism of inhibition of cell migration and how the compounds act in the cell cycle. Keywords: Combretum mellifluum, black propolis, cytotoxicity, spheroids, cell migration, cell cultureIntrodução: O câncer de mama afeta milhões de mulheres em todo o mundo e é o segunto tipo de câncer que mais acomete mulheres (atrás do câncer de pele não melanoma). Estima-se que mais de 600 mil novos casos de câncer ocorrerão anualmente entre 2020 até 2022.O uso de politerapia é comum no tratamento do câncer e tem a vantagem de maior eficácia nas diferentes subpopulações do tumor, além de evitar resistência medicamentosa. A associação de quimioterápicos padronizados com produtos naturais como isoflavonoides e terpenos são de grande importância, tendo em vista o potencial biológico em seus derivados. Objetivos: Avaliar a resposta celular à ação de compostos citotóxicos da biodiversidade Brasileira (própolis negra e Combretum Mellifluum) combinados ao quimioterápico doxorrubicina usando modelos de culturas celulares 2D e 3D de células de câncer de mama (MCF7). Métodos e Resultados: Os resultados de citotoxicidade em modelo 2D na linhagem neoplásica MCF-7 mostram GI50 de 4,089µg/mL para SBP (isoflavonoide oriundo da própolis negra) e 3,895µg/mL para SCM (triterpeno originado da C. mellifluum). Avaliou-se a citotoxicidade destes compostos após metabolização hepática in vitro. Observou-se que não houve inativação da substância e a atividade antiproliferativa foi preservada. Ambos compostos foram capazes de inibir a migração celular na linhagem potencialmente metastática, além de inibirem a formação de colônias de células neoplásicas ao serem associados com doxorrubicina. As amostras foram capazes de estimular o dano à membrana celular representado através da elevação dos níveis de TBARS e na resposta das defesas antioxidantes. Na investigação realizada em modelo 3D, percebe-se que o composto SCM quando associado a doxorrubicina é capaz de penetrar mais no esferoide formado. SBP e SCM foram capazes de fomentar o dano à membrana celular e interromper o ciclo celular na fase G1, antes que a célula adentrasse a fase S referente à síntese de material genético. Conclusões: Ambas substâncias tem efeito antiproliferativo contra câncer de mama em modelos 2D e 3D, in vitro, com potencial ainda a ser explorado no campo da biologia molecular. Palavras-chave: Combretum mellifluum, própolis negra, antiproliferativo, esferoides, migração celular, cultura celularFundação Universidade Federal de Mato Grosso do SulUFMSBrasilCOMPOSTOS CITOTÓXICOS DA BIODIVERSIDADE BRASILEIRA COMBINADOS À DOXORUBICINA NO TRATAMENTO DE CÂNCER DE MAMA EM MODELOS DE CULTURA CELULAR 2D E 3DCOMPOSTOS CITOTÓXICOS DA BIODIVERSIDADE BRASILEIRA COMBINADOS À DOXORUBICINA NO TRATAMENTO DE CÂNCER DE MAMA EM MODELOS DE CULTURA CELULAR 2D E 3Dinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisRenata Trentin PerdomoMARIAH OJEDAinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da UFMSinstname:Universidade Federal de Mato Grosso do Sul (UFMS)instacron:UFMSTHUMBNAILDEFESA MARIAH OJEDA PPG FARMACIA UFMS - COMPOSTOS CITOTÓXICOS DA BIODIVERSIDADE BRASILEIRA COMBINADOS À DOXORUBICINA NO TRATAMENTO DE CÂNCER DE MAMA EM MODELOS DE CULTURA CELULAR 2D E 3D.pdf.jpgDEFESA MARIAH OJEDA PPG FARMACIA UFMS - COMPOSTOS CITOTÓXICOS DA BIODIVERSIDADE BRASILEIRA COMBINADOS À DOXORUBICINA NO TRATAMENTO DE CÂNCER DE MAMA EM MODELOS DE CULTURA CELULAR 2D E 3D.pdf.jpgGenerated Thumbnailimage/jpeg1186https://repositorio.ufms.br/bitstream/123456789/3855/3/DEFESA%20MARIAH%20OJEDA%20PPG%20FARMACIA%20UFMS%20-%20COMPOSTOS%20CITOT%c3%93XICOS%20DA%20BIODIVERSIDADE%20BRASILEIRA%20COMBINADOS%20%c3%80%20DOXORUBICINA%20NO%20TRATAMENTO%20DE%20C%c3%82NCER%20DE%20MAMA%20EM%20MODELOS%20DE%20CULTURA%20CELULAR%202D%20E%203D.pdf.jpgb5f655dca5319afe7e3348f431e19b84MD53TEXTDEFESA MARIAH OJEDA PPG FARMACIA UFMS - COMPOSTOS CITOTÓXICOS DA BIODIVERSIDADE BRASILEIRA COMBINADOS À DOXORUBICINA NO TRATAMENTO DE CÂNCER DE MAMA EM MODELOS DE CULTURA CELULAR 2D E 3D.pdf.txtDEFESA MARIAH OJEDA PPG FARMACIA UFMS - COMPOSTOS CITOTÓXICOS DA BIODIVERSIDADE BRASILEIRA COMBINADOS À DOXORUBICINA NO TRATAMENTO DE CÂNCER DE MAMA EM MODELOS DE CULTURA CELULAR 2D E 3D.pdf.txtExtracted texttext/plain186927https://repositorio.ufms.br/bitstream/123456789/3855/2/DEFESA%20MARIAH%20OJEDA%20PPG%20FARMACIA%20UFMS%20-%20COMPOSTOS%20CITOT%c3%93XICOS%20DA%20BIODIVERSIDADE%20BRASILEIRA%20COMBINADOS%20%c3%80%20DOXORUBICINA%20NO%20TRATAMENTO%20DE%20C%c3%82NCER%20DE%20MAMA%20EM%20MODELOS%20DE%20CULTURA%20CELULAR%202D%20E%203D.pdf.txt7ba3a67e8829ba56e083c49cd0227dfdMD52ORIGINALDEFESA MARIAH OJEDA PPG FARMACIA UFMS - COMPOSTOS CITOTÓXICOS DA BIODIVERSIDADE BRASILEIRA COMBINADOS À DOXORUBICINA NO TRATAMENTO DE CÂNCER DE MAMA EM MODELOS DE CULTURA CELULAR 2D E 3D.pdfDEFESA MARIAH OJEDA PPG FARMACIA UFMS - COMPOSTOS CITOTÓXICOS DA BIODIVERSIDADE BRASILEIRA COMBINADOS À DOXORUBICINA NO TRATAMENTO DE CÂNCER DE MAMA EM MODELOS DE CULTURA CELULAR 2D E 3D.pdfapplication/pdf2526640https://repositorio.ufms.br/bitstream/123456789/3855/1/DEFESA%20MARIAH%20OJEDA%20PPG%20FARMACIA%20UFMS%20-%20COMPOSTOS%20CITOT%c3%93XICOS%20DA%20BIODIVERSIDADE%20BRASILEIRA%20COMBINADOS%20%c3%80%20DOXORUBICINA%20NO%20TRATAMENTO%20DE%20C%c3%82NCER%20DE%20MAMA%20EM%20MODELOS%20DE%20CULTURA%20CELULAR%202D%20E%203D.pdfd8f4a0abdd442f7b4be4de43a7820897MD51123456789/38552021-09-30 15:56:34.811oai:repositorio.ufms.br:123456789/3855Repositório InstitucionalPUBhttps://repositorio.ufms.br/oai/requestri.prograd@ufms.bropendoar:21242021-09-30T19:56:34Repositório Institucional da UFMS - Universidade Federal de Mato Grosso do Sul (UFMS)false
dc.title.pt_BR.fl_str_mv COMPOSTOS CITOTÓXICOS DA BIODIVERSIDADE BRASILEIRA COMBINADOS À DOXORUBICINA NO TRATAMENTO DE CÂNCER DE MAMA EM MODELOS DE CULTURA CELULAR 2D E 3D
title COMPOSTOS CITOTÓXICOS DA BIODIVERSIDADE BRASILEIRA COMBINADOS À DOXORUBICINA NO TRATAMENTO DE CÂNCER DE MAMA EM MODELOS DE CULTURA CELULAR 2D E 3D
spellingShingle COMPOSTOS CITOTÓXICOS DA BIODIVERSIDADE BRASILEIRA COMBINADOS À DOXORUBICINA NO TRATAMENTO DE CÂNCER DE MAMA EM MODELOS DE CULTURA CELULAR 2D E 3D
MARIAH OJEDA
COMPOSTOS CITOTÓXICOS DA BIODIVERSIDADE BRASILEIRA COMBINADOS À DOXORUBICINA NO TRATAMENTO DE CÂNCER DE MAMA EM MODELOS DE CULTURA CELULAR 2D E 3D
title_short COMPOSTOS CITOTÓXICOS DA BIODIVERSIDADE BRASILEIRA COMBINADOS À DOXORUBICINA NO TRATAMENTO DE CÂNCER DE MAMA EM MODELOS DE CULTURA CELULAR 2D E 3D
title_full COMPOSTOS CITOTÓXICOS DA BIODIVERSIDADE BRASILEIRA COMBINADOS À DOXORUBICINA NO TRATAMENTO DE CÂNCER DE MAMA EM MODELOS DE CULTURA CELULAR 2D E 3D
title_fullStr COMPOSTOS CITOTÓXICOS DA BIODIVERSIDADE BRASILEIRA COMBINADOS À DOXORUBICINA NO TRATAMENTO DE CÂNCER DE MAMA EM MODELOS DE CULTURA CELULAR 2D E 3D
title_full_unstemmed COMPOSTOS CITOTÓXICOS DA BIODIVERSIDADE BRASILEIRA COMBINADOS À DOXORUBICINA NO TRATAMENTO DE CÂNCER DE MAMA EM MODELOS DE CULTURA CELULAR 2D E 3D
title_sort COMPOSTOS CITOTÓXICOS DA BIODIVERSIDADE BRASILEIRA COMBINADOS À DOXORUBICINA NO TRATAMENTO DE CÂNCER DE MAMA EM MODELOS DE CULTURA CELULAR 2D E 3D
author MARIAH OJEDA
author_facet MARIAH OJEDA
author_role author
dc.contributor.advisor1.fl_str_mv Renata Trentin Perdomo
dc.contributor.author.fl_str_mv MARIAH OJEDA
contributor_str_mv Renata Trentin Perdomo
dc.subject.por.fl_str_mv COMPOSTOS CITOTÓXICOS DA BIODIVERSIDADE BRASILEIRA COMBINADOS À DOXORUBICINA NO TRATAMENTO DE CÂNCER DE MAMA EM MODELOS DE CULTURA CELULAR 2D E 3D
topic COMPOSTOS CITOTÓXICOS DA BIODIVERSIDADE BRASILEIRA COMBINADOS À DOXORUBICINA NO TRATAMENTO DE CÂNCER DE MAMA EM MODELOS DE CULTURA CELULAR 2D E 3D
description Introduction: Breast cancer affects millions of women worldwide and is the second type of cancer that most affects women (behind non-melanoma skin cancer). It is estimated that more than 600 thousand new cases of cancer will occur annually between 2020 until 2022. The use of polytherapy is common in the treatment of cancer and has the advantage of greater efficacy in the different subpopulations of the tumor, in addition to avoiding drug resistance. The association of standardized chemotherapy with natural products such as isoflavonoids and terpenes is of great importance, considering the biological potential in their derivatives. Objectives: To evaluate the action at the cellular level of cytotoxic compounds from Brazilian biodiversity (black propolis and C. Mellifluum) combined with chemotherapeutic agents doxorubicin in the Methodology and Results: The results of cytotoxicity in 2D model in the neoplastic lineage MCF-7 show an IC50 of 4.089µg/mL for SBP (isoflavonoid from black propolis) and 3.895µg/mL for SCM (triterpene originated from C. Mellifluum). The cytotoxicity of these compounds was evaluated after mimicking hepatic metabolism in vitro, observing that there was no inactivation of the substance and the cytotoxic activity was preserved. Both compounds were able to inhibit cell migration in potentially metastatic language, in addition to inhibiting the formation of colonies of neoplastic cells when associated with doxorubicin. The samples were able to stimulate cell membrane damage represented by the elevation of TBARS levels and the response of antioxidant defenses. In the investigation carried out in 3D model, it is noticed that the SCM compound when associated with doxorubicin can penetrate more into the formed spheroid. SBP and SCM were able to promote damage to the cell membrane and interrupt the cell cycle in the G1 phase, before the cell entered the S phase related to the synthesis of genetic material. Conclusions: The data found from the evaluation of the isolated compounds corroborate with that described in the literature regarding cytotoxic activity. It is necessary to advance the studies to better understand the mechanism of inhibition of cell migration and how the compounds act in the cell cycle. Keywords: Combretum mellifluum, black propolis, cytotoxicity, spheroids, cell migration, cell culture
publishDate 2021
dc.date.accessioned.fl_str_mv 2021-07-26T19:38:26Z
dc.date.available.fl_str_mv 2021-09-30T19:56:34Z
dc.date.issued.fl_str_mv 2021
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dc.publisher.country.fl_str_mv Brasil
publisher.none.fl_str_mv Fundação Universidade Federal de Mato Grosso do Sul
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