Niwa T, Swaneck G, Bradlow H L
Rockefeller University, New York, New York 10021.
Steroids. 1994 Sep;59(9):523-7. doi: 10.1016/0039-128x(94)90070-1.
In mammals, estradiol (E2) metabolism primarily involves mutually exclusive hydroxylation at either C-2 or C-16 alpha. We have previously reported a consistent increase in the C-16 alpha 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-16 alpha. 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.
在哺乳动物中，雌二醇（E2）代谢主要涉及在C-2或C-16α处相互排斥的羟基化作用。我们之前报道过，在人类乳腺癌以及乳腺肿瘤水平较高的小鼠品系中，C-16α羟基化活性持续增加。在此我们表明，膳食化合物吲哚-3-甲醇（I3C）使培养的MCF-7细胞中的C-2羟基化增加了五倍，但对C-16α处的反应影响极小。由于I3C诱导的E2代谢变化导致的代谢物比例与乳腺癌女性中观察到的相反，我们分别研究了这种转变是否赋予雌激素靶细胞抗肿瘤优势。I3C在MCF-7细胞中对雌二醇代谢诱导的优先变化与其在小鼠中的抗肿瘤性相似。这些结果表明，通过C-2途径的雌二醇代谢变化可能在降低女性患乳腺癌风险方面发挥重要作用。吲哚-2-甲醇作为一种化学物质以及十字花科蔬菜的膳食成分很容易获得。可行的饮食改变有望在预防乳腺癌和其他激素依赖性癌症方面具有临床应用价值。
