Estudo sobre o potencial antitumoral de derivados esterificados do ácido cumárico
Arquivos
Data
2022
Autores
Martins, Joana Irisvânia Carmo 
Orientadores
Keller, Alexandre de Castro
Tipo
Trabalho de conclusão de curso
Título da Revista
ISSN da Revista
Título de Volume
Resumo
O câncer ainda representa um dos maiores desafios da medicina moderna, sendo que as terapias disponíveis envolvem diversos efeitos colaterais e nem sempre são acessíveis à população em geral. Nesse sentido, o estudo de compostos de origem vegetal para o tratamento do câncer vai de encontro com a busca por terapias eficientes e de baixo custo financeiro. Como muitas vezes os efeitos biológicos são alcançados apenas em altas concentrações, a modificação química desses compostos naturais surge como uma alternativa para potencializar seu emprego terapêutico. Nesse sentido, o objetivo do nosso trabalho foi determinar o potencial antitumoral de dois ésteres cumaratos, obtidos da esterificação do ácido cumárico (p-CA), um ácido fenólico encontrado em plantas e cogumelos. Para tanto, células de melanoma murino (B16-F10) ou humano (SK-MEL-25) foram tratadas com etil p-cumarato (composto 1) e n-butil p-cumarato (composto 2). A análise de viabilidade celular por dosagem de lactato desidrogenase e coloração de células viáveis com cristal violeta demonstrou que os compostos apresentam ação citotóxica em concentrações acima de 100 μM, enquanto o p-CA apresenta esse efeito descrito apenas em concentrações acima de 1000 μM. Além disso, análises da proliferação e do ciclo celular por citometria de fluxo indicam que ambos os compostos apresentam atividade citostática sobre ambas as linhagens celulares. Mais ainda, em ensaios ex vivo, os compostos derivados do p-CA não apresentaram impacto negativo sobre a viabilidade de células do baço de animais C57/Bl6, sendo um dos compostos capaz de aumentar a expressão de CD69, uma molécula indicativa de ativação precoce, em linfócitos T e B e células NK. Portanto, nossos dados mostram que os compostos derivados quimicamente do p-CA apresentam atividade citotóxica e citostática sobre duas linhagens diferentes de melanoma, sem impactar negativamente a viabilidade de células imunológicas. Uma vez que além da atividade antitumoral, um desses compostos pode contribuir para ativação do sistema imunológico, pode-se dizer que essas moléculas podem colaborar para melhorar o prognóstico de pacientes com o câncer, inclusive complementando outras terapias.
Cancer still represents one of the greatest challenges of modern medicine, the available therapies involve several side effects and are not always accessible to the general population. In this sense, the study of compounds of plant origin for the treatment of cancer meets the search for efficient and low-cost therapies. As biological effects are often achieved only at high concentrations, chemical modification of these natural compounds appears as an alternative to enhance their therapeutic use. Hence, the objective of our work was to determine the antitumor potential of two coumarate esters, obtained from the esterification of coumaric acid (p-CA), a phenolic acid found in plants and mushrooms. To this end, murine (B16-F10) or human (SK-MEL-25) melanoma cells were treated with ethyl p-coumarate (compound 1) and n-butyl p-coumarate (compound 2). Cell viability analysis by measurement of lactate dehydrogenase and staining of viable cells with crystal violet showed that the compounds have cytotoxic action at concentrations above 100 μM, while p-CA has this described effect only at concentrations above 1000 μM. Furthermore, analyzes of proliferation and cell cycle by flow cytometry indicate that both compounds have cytostatic activity on both cell lines. In addition, in ex vivo assays, compounds derived from p-CA did not have a negative impact on the viability of spleen cells from C57/Bl6 animals, being one of the compounds capable of increasing the expression of CD69, a molecule indicative of early activation, in T and B lymphocytes and NK cells. Therefore, our data show that compounds chemically derived from p-CA have cytotoxic and cytostatic activity against two different melanoma cell lines, without negatively impacting the viability of immune cells. In conclusion, besides to the antitumor activity, one of these compounds can contribute to the activation of the immune system, it can be said that these molecules can collaborate to improve the prognosis of cancer patients, including complementing other therapies.
Cancer still represents one of the greatest challenges of modern medicine, the available therapies involve several side effects and are not always accessible to the general population. In this sense, the study of compounds of plant origin for the treatment of cancer meets the search for efficient and low-cost therapies. As biological effects are often achieved only at high concentrations, chemical modification of these natural compounds appears as an alternative to enhance their therapeutic use. Hence, the objective of our work was to determine the antitumor potential of two coumarate esters, obtained from the esterification of coumaric acid (p-CA), a phenolic acid found in plants and mushrooms. To this end, murine (B16-F10) or human (SK-MEL-25) melanoma cells were treated with ethyl p-coumarate (compound 1) and n-butyl p-coumarate (compound 2). Cell viability analysis by measurement of lactate dehydrogenase and staining of viable cells with crystal violet showed that the compounds have cytotoxic action at concentrations above 100 μM, while p-CA has this described effect only at concentrations above 1000 μM. Furthermore, analyzes of proliferation and cell cycle by flow cytometry indicate that both compounds have cytostatic activity on both cell lines. In addition, in ex vivo assays, compounds derived from p-CA did not have a negative impact on the viability of spleen cells from C57/Bl6 animals, being one of the compounds capable of increasing the expression of CD69, a molecule indicative of early activation, in T and B lymphocytes and NK cells. Therefore, our data show that compounds chemically derived from p-CA have cytotoxic and cytostatic activity against two different melanoma cell lines, without negatively impacting the viability of immune cells. In conclusion, besides to the antitumor activity, one of these compounds can contribute to the activation of the immune system, it can be said that these molecules can collaborate to improve the prognosis of cancer patients, including complementing other therapies.