In mammals, estradiol (E2) metabolism primarily involves mutually exclusive hydroxylation at either C-2 or C-16α. We have previously reported a consistent increase in the C-16α hydroxylation activity in human breast cancer and in mouse strains with high levels of mammary tumors. Here we show that the dietary compound indole-3-carbinol (I3C) increases C-2 hydroxylation five-fold in MCF-7 cells in culture but has minimal effect on the reaction at C-16α. Because I3C-induced changes in E2 metabolism result in a metabolite ratio inverse to that observed in women with breast cancer we have separately examined whether this shift conferred an anti-tumorigenic advantage to estrogen target cells. The preferential changes induced by I3C on estradiol metabolism in MCF-7 cells parallel its anti-tumorigenicity in mice. These results suggest that changes in the metabolism of estradiol via the C-2 pathway might play a significant role in decreasing risk for breast cancer in women. Indole-2-carbinol is readily available as a chemical and as a dietary component of cruciferous vegetables. Feasible dietary changes show promise of having clinical utility in the prevention of breast cancer and other hormone-dependent cancers.
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