Effect of the supplementation with different selenium dietary sources on the evolution of mammary tumor induced by 4T1 cells inoculation in mice

Abstract

Breast cancer is the most prevalent type in women from Brazil and worldwide. Despite the advances in early diagnosis and treatment methods, this kind of cancer still presents high morbidity and mortality. Some micronutrients have been studied because of their potential effect as inhibitors of malignant neoplasms evolution. The association between minerals (micronutrients that are essential for cellular functions) and breast cancer has not been much studied yet and, among these minerals, selenium (Se) stands out. This study aimed to evaluate the effect of the supplementation with different Se sources on the evolution of experimental mammary carcinoma induced by 4T1 cells inoculation in Balb-c female mice. Thirty animals were selected and each mice received a subcutaneous injection on the flank for tumor cells inoculation (1 x 10 6 4T1 cells diluted in 0.1 mL of phosphate buffered saline). Tumor growth was measured every 24 hours and at the fifth day all animals had palpable tumors. From then on, animals were randomly distributed into three experimental groups receiving respectively: diet containing recommended Se levels (Se-adequate) 0.15 ppm; diet enriched with selenomethionine (SeMet) 1.4 ppm; or diet enriched with Brazilian nuts (Se-Nuts) 1.4 ppm for 28 days. During that period, tumor growth was evaluated every 48 hours. At the 29 th day animals were euthanized for Se blood concentration analysis and for quantification of hepatic glutathione peroxidase (GPx) enzymatic activity. At the first 8 days after initiation of dietary treatment, tumor growth was significantly lower (p < 0.05) in Se-supplemented groups (SeMet and Se-Nuts) when compared to Se-adequate diet. However, the protection was not maintained at the following weeks and there was no effect of diets on tumor total growth through 28 days. SeMet group presented average Se blood concentration of 0.507 µg/mL, significantly higher (p < 0.05) than the Se-adequate group (0.342 µg/mL), but with no difference from Se-Nuts group (0.461 µg/mL), which presented an intermediate value. Average hepatic GPx enzyme activities in the Se-adequate, SeMet and Se-Nuts groups were, respectively, 6663.583, 7486.480 e 7862.332 nmo/min/mL, and no significant difference was observed between them. There was no correlation between Se blood concentration, GPx activity and tumor growth. It was concluded that dietary Se supplementation (by both SeMet or Brazilian nuts) reduced tumor growth during the initial stages. Additional studies are encouraged in order to elucidate mechanisms promoted by Se intake in the different carcinogenic stages