Preferential Induction of CYP1A1 over CYP1B1 in Human Breast Cancer MCF-7 Cells after Exposure to Berberine
Preferential Induction of CYP1A1 over CYP1B1 in Human Breast Cancer MCF-7 Cells after Exposure to Berberine
复制标题
接触小檗碱后人乳腺癌 MCF-7 细胞中 CYP1A1 优先诱导 CYP1A1 优于 CYP1B1
DOI：
10.7314/apjcp.2014.15.1.495
复制
发表时间：
2014-01-01
影响因子：
--
通讯作者：
Zhou, Hong-Hao
中科院分区：
文献类型：
--
作者：
Wen, Chun-Jie;Wu, Lan-Xiang;Zhou, Hong-Hao
雌激素被认为是乳腺癌的主要危险因素，雌激素的致癌潜力可能归因于代谢过程中形成的衍生物引起的DNA修饰。17β-雌二醇(E-2)是女性体内主要的类固醇雌激素，其代谢途径主要有两条：2-羟基雌二醇(2-OHE-2)和4-羟基雌二醇(4-OHE-2)分别通过细胞色素P450(CYP)1a1和1b1作用形成。以往的报道表明，2-OHE-2具有潜在的保护作用，而4-OHE-2具有遗传毒性并具有很强的致癌活性。因此，2-OHE-2/4-OHE-2的比值是决定E-2对乳腺细胞毒性的关键决定因素。在本研究中，我们研究了黄连素对乳腺癌MCF-7细胞雌激素代谢酶CYP1A1和CYP1B1表达谱的影响。黄连素处理可显著诱导这两种形式的基因表达，但随着处理剂量的增加，诱导产生的细胞色素P4501A1和细胞色素P1B1B1mRNA的比例接近16和52倍。此外，黄连素显著增加MCF-7细胞中的CYP1A1蛋白水平，但不影响CYP1B1蛋白水平。综上所述，我们首次报道了黄连素可能通过改变细胞色素P1A1/细胞色素P1B1的比例对乳腺癌起到保护作用，可以将乳腺癌MCF-7细胞中的E-2代谢重定向到一个更具保护作用的途径。
Estrogens are considered the major breast cancer risk factor, and the carcinogenic potential of estrogens might be attributed to DNA modification caused by derivatives formed during metabolism. 17 beta-estradiol (E-2), the main steroidal estrogen present in women, is metabolized via two major pathways: formation of 2-hydroxyestradiol (2-OH E-2) and 4-hydroxyestradiol (4-OH E-2) through the action of cytochrome P450 (CYP) 1A1 and 1B1, respectively. Previous reports suggested that 2-OH E-2 has putative protective effects, while 4-OH E-2 is genotoxic and has potent carcinogenic activity. Thus, the ratio of 2-OH E-2/4-OH E-2 is a critical determinant of the toxicity of E-2 in mammary cells. In the present study, we investigated the effects of berberine on the expression profile of the estrogen metabolizing enzymes CYP1A1 and CYP1B1 in breast cancer MCF-7 cells. Berberine treatment produced significant induction of both forms at the level of mRNA expression, but with increased doses produced 16 similar to to 52 similar to fold greater induction of CYP1A1 mRNA over CYP1B1 mRNA. Furthermore, berberine dramatically increased CYP1A1 protein levels but did not influence CYP1B1 protein levels in MCF-7 cells. In conclusion, we present the first report to show that berberine may provide protection against breast cancer by altering the ratio of CYP1A1/CYP1B1, could redirect E-2 metabolism in a more protective pathway in breast cancer MCF-7 cells.