title: Genistein Induces Cytochrome P450 1B1 Gene Expression and Cell Proliferation in Human Breast Cancer MCF-7 Cells.
abstract: 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.
authors.affiliation: Mercer University School of Medicine, Macon, Georgia; The University of Georgia, Athens, Georgia, USA.
authors.forename: Yinan K
authors.initials: YK
authors.lastname: Wei
authors.affiliation: Mercer University School of Medicine, Macon, Georgia, USA.
authors.forename: Irene
authors.initials: I
authors.lastname: Gamra
authors.affiliation: Mercer University School of Medicine, Macon, Georgia, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Davenport
authors.affiliation: Mercer University School of Medicine, Macon, Georgia, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Lester
authors.affiliation: Mercer University School of Medicine, Macon, Georgia, USA; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Mercer University School of Medicine.
authors.forename: Yudan
authors.initials: Y
authors.lastname: Wei
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D002274:Carcinogens, Environmental; D017382:Reactive Oxygen Species; D015127:9,10-Dimethyl-1,2-benzanthracene; D019833:Genistein; D065633:Cytochrome P-450 CYP1B1