ABSTRACT
Cancer constitutes the second main mortality cause in the world, after cardiovascular diseases. In spite of the progresses in the chemotherapeutics treatments, many patients fail chemotherapy, mainly because of side effects or multi-drugs resistance, proving the need and importance of the research for new molecules with anticancer activity, more effective and with smaller adverse effects. Various compounds derived from plant secondary metabolites are commonly used in the chemotherapy against cancer and the natural products play an important role in the research for new molecules. Among several molecules of natural origin evaluated by MTT assay in murine tumor cell lines [breast (LM3) and lung (LP07)] the quinona-methide triterpenes tingenone and pristimerin showed marked cytotoxic activity presenting IC50 around 2 and 5 µM respectively. The structure-activity relationship suggests that rings A and B containing an α, ß-unsaturated carbonyl group are essential for the observed cytotoxic activity. The interaction between these positions and acetylcisteyne residues suggests a probable mechanism of action. The in vitro mutagenic activity was also evaluated by the Salmonella microsome assay (Ames test) for pristimerin and tingenone with and without metabolic activation (S9) in the strains TA98, TA97a, TA100 and TA102, none of which showed mutagenic potential in any strains. Estrogenic and anti-estrogenic activities were also studied by the e-screen assay in MCF-7 cells with negative results. The present data point to the importance of pristimerin and tingenone as representative of an emerging class of potential anticancer chemicals.
ABSTRACT
O câncer de mama é uma doença que afeta principalmente as mulheres e segundo as estatísticas esta vem aumentando com certa frequência nos países ocidentais, e isto tem preocupado a comunidade científica. Esta doença está associada a diversos fatores de risco, sendo a dieta um fator que tem demonstrado relação com a promoção de câncer de mama. Uma alimentação rica em substância funcional tem sido alvo de atenção, pois os fitoestrógenos têm mostrado através de estudos experimentais, propriedades benéficas à saúde, e parece contribuir para a redução do risco de câncer de mama. Alimentos como a semente de linhaça tem sido objeto de estudo, já que contêm substâncias consideradas como quimioprotetora e sua estrutura química assemelha-se ao estrogênio humano e compete com este pelo seu sítio de ligação. De acordo com os estudos experimentais, realizados com animais e humanos, a semente de linhaça é rica em lignana e outros componentes, que apresentaram ter efeito fracamente estrogênico e antiestrogênico, mostrando exercer influência na diminuição do risco de câncer de mama.
The breast cancer is a disease that affects especially women, and according to statistics, this is increasing with certain frequency in western country and it has been concerning the scientific society. This disease is associated with various factors of risk, and diets have being considered a factor that has promoted breast cancer. Food rich in functional substances has drawn attention, because phytoestrogens have showed, through experimental studies, beneficial properties for health and appeared to contribute for the decrease of breast cancer risk. Food with flaxseed has been object of study, because it contains substances called chemoprotective and its chemistry structure resembles human estrogens and competes with its link site. According to the experimental studies made in animals and humans, flaxseed is rich in lignans and other components, that seem to have weak estrogenic/antiestrogenic effect showing to exert influence in the decreasing of breast cancer risk.