Phenethyl Isothiocyanate in Breast Cancer Prevention

摘要

Our hypothesis is that PEITC is an effective preventive agent in breast cancer. Although a number of mechanisms may be involved, one mechanism that has not been explored is the potential for PEITC to alter the synthesis and elimination of estrogens. Our specific aims are: to evaluate the efficacy of dietary PEITC, at relevant doses, in preventing or delaying the onset of breast cancer in estrogen-dependent breast cancer animal models; to evaluate the effects of PEITC on 17beta-estradiol (E2) and metabolite concentrations in plasma and tumor samples; and to determine changes in enzyme activity and/or mRNA/protein expression in tumor and liver samples, for metabolic pathways which may be altered based on the E2 and E2 metabolite profiles. Our studies have characterized the pharmacokinetics of PEITC in rats, developed a LC/MS/MS assay for l7Beta-estradiol, and demonstrated in preliminary studies that PEITC can alter estrogen metabolism in human - mammary and breast cancer cells and in rat liver. Additionally, we found that low concentrations of PEITC can alter the expression of some estrogen-responsive genes important in breast cancer. These studies provide new findings regarding the chemopreventive effects of the dietary compound PEITC in estrogen-dependent breast cancer.