期刊
MOLECULAR CARCINOGENESIS
卷 52, 期 7, 页码 514-525出版社
WILEY
DOI: 10.1002/mc.21886
关键词
vitamin E; tocopherol; breast cancer; estrogen receptor; peroxisome proliferator-activated receptor
资金
- NIH [R03 CA141756]
- Trustees Research Fellowship Program at Rutgers, The State University of New Jersey
- NIEHS Center [P30 ES005022]
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 10wk. 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. (c) 2012 Wiley Periodicals, Inc.
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