Genistein Induces Cytochrome P450 1B1 Gene Expression and Cell Proliferation in Human Breast Cancer MCF-7 Cells.

Cytochrome P450 1B1 (CYP1B1) plays an important role in breast cancer development and progression by bioactivating endogenous estrogens and environmental carcinogens. In this study, we examined the effect of the soy isoflavone genistein on CYP1B1 gene expression, reactive oxygen species (ROS) production, and cell proliferation in human breast cancer MCF-7 cells. Real-time reverse transcription polymerase chain reaction (RT-PCR) analysis showed a dose-dependent induction of CYP1B1 gene expression in the cells treated with 5 and 25 μM of genistein. Genistein at 5 μM exhibited a synergistic effect on the CYP1B1 mRNA level induced by the environmental carcinogen 7,12-dimethylbenz[a]anthracene. We also found that genistein at 5 μM increased cellular levels of ROS and stimulated cell proliferation starting from the second day of culture. This study suggests that physiological concentrations of genistein stimulate ROS production and breast cancer cell proliferation through the induction of CYP1B1 gene expression. More extensive studies are warranted to further characterize the role of genistein and the CYP1B1 enzyme in human breast carcinogenesis.