Ação da própolis associada ao docetaxel sobre células de câncer de mama e sobre monócitos humanos
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2021-04-01
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Universidade Estadual Paulista (Unesp)
Resumo
Câncer é um grupo de doenças que atingem pessoas em todo o mundo, causando milhões de morte anualmente. Docetaxel (DTX) é uma das abordagens terapêuticas mais utilizadas contra cânceres de mama. Todavia, quimioterápicos podem apresentar efeitos colaterais, tais como toxicidade e imunossupressão, podendo levar ao aparecimento de infecções. Para minimizar os efeitos colaterais causados pela quimioterapia, tem-se investigado a associação entre quimioterápicos e produtos naturais. Própolis é um produto apícola que apresenta muitas atividades farmacológicas. Neste trabalho, investigamos a ação citotóxica e imunomoduladora de uma associação entre extrato etanólico de própolis (EEP) e docetaxel (DTX) sobre a linhagem celular MCF-7 de câncer de mama e sobre monócitos obtidos de mulheres saudáveis. O potencial citotóxico da combinação EEP+DTX sobre a linhagem MCF-7 e monócitos foi verificado por ensaio de viabilidade celular (MTT); e o tipo de morte celular (apoptose/necrose) foi avaliado por citometria de fluxo. Os efeitos de EEP, DTX e EEP+DTX sobre a migração e invasão das células MCF-7 também foram investigados. A produção das citocinas IL-1β, TNF-α, IL-6 e IL-10 por monócitos foi verificada por ELISA; a expressão dos marcadores celulares HLA-DR, CD80, TLR-2 e TLR-4 foi avaliada por citometria de fluxo. Também foi avaliada a atividade fungicida de monócitos contra Candida albicans e a produção de espécies reativas do oxigênio (EROs). O impacto do sobrenadante de monócitos tratados sobre a viabilidade, migração e invasão das células tumorais também foi investigado. A associação EEP (25 μg/mL) + DTX (10 nM) potencializou a ação citotóxica do quimioterápico contra a linhagem MCF-7, induzindo morte celular por necrose e impedindo a migração dessas células. EEP+DTX não afetou a viabilidade de monócitos humanos, estimulou a expressão de HLA-DR, a produção de TNF-α e IL-6, restaurou a atividade candidacida e reduziu o estresse oxidativo dos monócitos. Tais resultados indicam que EEP em combinação com baixas concentrações de DTX afetou a viabilidade e migração de células MCF-7 in vitro, e favoreceu alguns parâmetros imunológicos relacionados às funções dos monócitos. Estes são achados novos e relevantes que merecem mais investigações devido às suas implicações práticas, a fim de propor uma nova abordagem terapêutica na Medicina Alternativa e Complementar para pacientes oncológicos.
Cancer widely affects the world population, with millions of deaths registered anually. Docetaxel (DTX) is one of the therapeutic approaches against breast cancer. Nevertheless, chemotherapy may exert side effects like toxicity and immunosuppression, leading to infections. In an attempt to reduce the adverse effects caused by chemotherapy, the dual application of medicines and natural products has been investigated. Propolis is made by honeybees showing many pharmacological properties. In this study, we investigated the cytotoxic and immunomodulatory effects of the ethanolic extract of propolis (EEP) in combination with DTX on breast cancer MCF-7 cells and on monocytes from healthy female blood donors. The cytotoxic potential of EEP+DTX was assessed by MTT assay and the type of tumor cell death (apoptosis/necrosis) was evaluated by flow cytometry. The effects of EEP, DTX and their combination on the migration and invasion of MCF-7 cells were observed. Cytokine production (IL-1β, TNF-α, IL-6 and IL-10) by monocytes was assessed by ELISA; the expression of cell surface markers (HLA-DR, CD80, TLR-2 and TLR-4) was verified by flow cytometry. We also investigated the fungicidal activity of monocytes against Candida albicans and reactive oxygen species (ROS) generation. Finally, the impact of the supernatants of treated monocytes in the viability, migration and invasiveness of tumor cells was assessed. EEP (25 μg/mL) + DTX (10 nM) enhanced the cytotoxic action of DTX alone against MCF-7 cells by inducing necrosis and inhibiting their migratory ability. EEP+DTX exerted no cytotoxic action in monocytes and stimulated HLA-DR expression, TNF-α and IL-6 production, exerted an immunorestorative action in the fungicidal activity and reduced the oxidative stress of monocytes. Data indicated that EEP in combination with lower concentrations of DTX affected the viability and migration of MCF-7 cells in vitro, and improved some immunological parameters related to monocyte functions. This is a new and relevant finding that deserves further investigation due to its practical implications, proposing a new therapeutic approach for oncologic patients in Complementary and Alternative Medicine
Cancer widely affects the world population, with millions of deaths registered anually. Docetaxel (DTX) is one of the therapeutic approaches against breast cancer. Nevertheless, chemotherapy may exert side effects like toxicity and immunosuppression, leading to infections. In an attempt to reduce the adverse effects caused by chemotherapy, the dual application of medicines and natural products has been investigated. Propolis is made by honeybees showing many pharmacological properties. In this study, we investigated the cytotoxic and immunomodulatory effects of the ethanolic extract of propolis (EEP) in combination with DTX on breast cancer MCF-7 cells and on monocytes from healthy female blood donors. The cytotoxic potential of EEP+DTX was assessed by MTT assay and the type of tumor cell death (apoptosis/necrosis) was evaluated by flow cytometry. The effects of EEP, DTX and their combination on the migration and invasion of MCF-7 cells were observed. Cytokine production (IL-1β, TNF-α, IL-6 and IL-10) by monocytes was assessed by ELISA; the expression of cell surface markers (HLA-DR, CD80, TLR-2 and TLR-4) was verified by flow cytometry. We also investigated the fungicidal activity of monocytes against Candida albicans and reactive oxygen species (ROS) generation. Finally, the impact of the supernatants of treated monocytes in the viability, migration and invasiveness of tumor cells was assessed. EEP (25 μg/mL) + DTX (10 nM) enhanced the cytotoxic action of DTX alone against MCF-7 cells by inducing necrosis and inhibiting their migratory ability. EEP+DTX exerted no cytotoxic action in monocytes and stimulated HLA-DR expression, TNF-α and IL-6 production, exerted an immunorestorative action in the fungicidal activity and reduced the oxidative stress of monocytes. Data indicated that EEP in combination with lower concentrations of DTX affected the viability and migration of MCF-7 cells in vitro, and improved some immunological parameters related to monocyte functions. This is a new and relevant finding that deserves further investigation due to its practical implications, proposing a new therapeutic approach for oncologic patients in Complementary and Alternative Medicine
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Palavras-chave
Própolis, Docetaxel, Câncer de mama, Imunomodulação, Breast cancer, Immunomodulation