Dietary tocopherols inhibit cell proliferation, regulate expression of ER?, PPAR?, and Nrf2, and decrease serum inflammatory markers during the development of mammary hyperplasia.

ABSTRACT: Previous clinical and epidemiological studies of vitamin E have used primarily ?-tocopherol for the prevention of cancer. However, ?-tocopherol has demonstrated greater anti-inflammatory and anti-tumor activity than ?-tocopherol in several animal models of cancer. This study assessed the potential chemopreventive activities of a tocopherol mixture containing 58% ?-tocopherol (?-TmT) in an established rodent model of mammary carcinogenesis. Female ACI rats were utilized due to their sensitivity to 17?-estradiol (E2 ) to induce mammary hyperplasia and neoplasia. The rats were implanted subcutaneously with sustained release E2 pellets and given dietary 0.3% or 0.5% ?-TmT for 2 or 10?wk. Serum E2 levels were significantly reduced by the treatment with 0.5% ?-TmT. Serum levels of inflammatory markers, prostaglandin E2 and 8-isoprostane, were suppressed by ?-TmT treatment. Histology of mammary glands showed evidence of epithelial hyperplasia in E2 -treated rats. Immunohistochemical analysis of the mammary glands revealed a decrease in proliferating cell nuclear antigen (PCNA), cyclooxygenase-2 (COX-2), and estrogen receptor ? (ER?), while there was an increase in cleaved-caspase 3, peroxisome proliferator-activated receptor ? (PPAR?), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in ?-TmT-treated rats. In addition, treatment with ?-TmT resulted in a decrease in the expression of ER? mRNA, whereas mRNA levels of ER? and PPAR? were increased. In conclusion, ?-TmT was shown to suppress inflammatory markers, inhibit E2 -induced cell proliferation, and upregulate PPAR? and Nrf2 expression in mammary hyperplasia, suggesting that ?-TmT may be a promising agent for human breast cancer prevention.

SUBMITTER: Smolarek AK 

PROVIDER: S-EPMC3374909 | biostudies-other | 2013 Jul

REPOSITORIES: biostudies-other