Isothiocyanates and breast cancer prevention
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Isothiocyanates, a class of anti-cancer agents, are derived from cruciferous vegetables such as broccoli, cabbage and watercress, and have demonstrated chemopreventive activity in a number of cancer models and epidemiologic studies. Breast cancer, the most common cancer affecting women is known to be estrogen dependent. Phenethyl isothiocyanate (PEITC) has high bioavailability and low toxicity and has been shown to inhibit Phase I enzymes and induce Phase II enzymes both in vivo and in vitro. The overall hypothesis of this work is that PEITC is a breast cancer preventive agent, acting at least in part through changes in the synthesis or metabolism of 17β-estradiol. To test this, we examined the effect of oral PEITC on the progression of breast cancer in a N-methyl nitrosourea (NMU) induced model of estrogen dependent breast cancer in female Sprague Dawley rats. We examined the effects of this dietary agent on hepatic gene expression of metabolic enzymes responsible for the metabolism of xenobiotics and carcinogens. To examine the studies on human cells, we investigated the effects of PEITC on estradiol concentrations in MCF7 cells, an estrogen dependent breast cancer cell line. Finally, we compared the differences in gene expression between MCF7 and normal human mammary epithelial cells (HMEC), to gain insight into the effects of PEITC in normal and cancerous cells. In conclusion, we report for the first time, that oral PEITC demonstrates chemopreventive activity in NMU-induced breast cancer, and decreases the gene expression of N-methyl transferase, an enzyme recently shown to be a serum biomarker in several cancers. In vitro we were able to establish that low concentrations of PEITC were able to reduce intracellular estradiol concentrations, suggesting a possible beneficial role of the dietary agent in estrogen dependent breast cancer.