Abstract 1851: Dietary mixed tocopherols inhibit cell proliferation in mammary hyperplasia, suppress the expression of inflammatory markers, and upregulate PPARγ

Abstract

Abstract Dietary intake of vitamin E, a fat-soluble vitamin, has been suggested to reduce cancer risk because of antioxidant properties. There are eight different forms of vitamin E which include four tocopherols (with a saturated phytyl tail) and four tocotrienols (with an unsaturated isoprenoid side chain) designated as α, β, γ, and Δ variants. Previous clinical and epidemiological studies on vitamin E and cancer have focused on α-tocopherol. However, γ-tocopherol has demonstrated greater anti-inflammatory and anti-tumor activity than α-tocopherol. This study assessed the potential chemopreventive activities of a tocopherol mixture containing 58% γ-tocopherol (γ-TmT) in an established rodent model of mammary carcinogenesis. Female ACI rats were utilized due to their sensitivity to 17β-estradiol to induce mammary hyperplasia and eventually mammary tumors. The rats were implanted subcutaneously with estradiol (E2) pellets containing 2.5 mg of E2 and given 0.3% or 0.5% γ-TmT in the diet for 2 or 10 weeks. Serum E2 levels were significantly reduced by the treatment with 0.5% γ-TmT. Serum levels of anti-inflammatory markers, prostaglandin E2 and 8-isoprostane, were suppressed by γ-TmT treatment. Histology of mammary glands showed evidence of epithelial hyperplasia in E2 treated rats. Immunohistochemical analysis revealed a decrease in estrogen receptor α (ERα) and proliferating cell nuclear antigen (PCNA), and an increase in cleaved-caspase3 and peroxisome proliferator-activated receptor γ (PPARγ) in the γ-TmT treated rats, indicating that tocopherol treatment inhibits cell proliferation and induces apoptosis. Treatment with γ-TmT resulted in a decrease in the expression of ERα mRNA, while ERβ and PPARγ mRNA levels were increased. These data suggest that γ-TmT inhibits the cell proliferation in mammary hyperplasia, suppresses the expression of inflammatory markers, and upregulates PPARγ. In conclusion, γ-TmT may be a promising agent for human breast cancer prevention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1851. doi:10.1158/1538-7445.AM2011-1851