Wei Yinan K, Gamra Irene, Davenport Andrew, Lester Richard, Zhao Lijun, Wei Yudan
Mercer University School of Medicine, Macon, Georgia; The University of Georgia, Athens, Georgia, USA.
Mercer University School of Medicine, Macon, Georgia, USA.
J Environ Pathol Toxicol Oncol. 2015;34(2):153-9. doi: 10.1615/jenvironpatholtoxicoloncol.2015013315.
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.
细胞色素P450 1B1（CYP1B1）通过对内源性雌激素和环境致癌物进行生物活化，在乳腺癌的发生和发展中发挥重要作用。在本研究中，我们检测了大豆异黄酮染料木黄酮对人乳腺癌MCF-7细胞中CYP1B1基因表达、活性氧（ROS）生成及细胞增殖的影响。实时逆转录聚合酶链反应（RT-PCR）分析显示，用5 μM和25 μM染料木黄酮处理的细胞中，CYP1B1基因表达呈剂量依赖性诱导。5 μM的染料木黄酮对环境致癌物7,12-二甲基苯并[a]蒽诱导的CYP1B1 mRNA水平具有协同作用。我们还发现，5 μM的染料木黄酮从培养第二天起可提高细胞内ROS水平并刺激细胞增殖。本研究表明，生理浓度的染料木黄酮通过诱导CYP1B1基因表达刺激ROS生成和乳腺癌细胞增殖。有必要进行更广泛的研究，以进一步明确染料木黄酮和CYP1B1酶在人类乳腺癌发生中的作用。
