Soy isoflavones decrease the catechol-O-methyltransferase-mediated inactivation of 4-hydroxyestradiol in cultured MCF-7 cells.

The tissue concentrations of the female sex hormone 17beta-estradiol (E2) and its reactive catechol metabolites such as 4-hydroxyestradiol (4-HO-E2) play important roles in hormonal carcinogenesis. They are influenced by the activity of local enzymes involved in the metabolic activation and inactivation of E2. In the mammary gland, catechol estrogens are predominately inactivated by catechol-O-methyltransferase (COMT). Food supplements containing the soy isoflavones genistein and daidzein are consumed because they are believed to protect from breast cancer; however, this proposed benefit is controversial. The aim of the present study was to investigate the influence of soy isoflavones on the gene expression and activity of COMT in cultured human mammary adenocarcinoma MCF-7 cells. Levels of COMT messenger RNA (mRNA) were determined by reverse transcription/competitive polymerase chain reaction and COMT activity was determined by high-performance liquid chromatography analysis of the methylation products of both the model substrate quercetin and the physiological relevant substrate 4-HO-E2. Our study demonstrates for the first time that soy isoflavones at hormonally active concentrations cause a significant reduction of both COMT mRNA levels and COMT activity as well as of the methylation of 4-HO-E2. Experiments using the estrogen receptor (ER) antagonist ICI 182,780 support a role of the ER in the isoflavone-induced down-regulation of COMT expression. Thus, this study not only demonstrates that hormonally active concentrations of soy isoflavones inhibit the detoxification of catechols in this human breast cancer cell line but also implies that diet might influence COMT activity to a greater extent than heretofore recognized.