Baicalein has protective effects on the 17β-estradiol-induced transformation of breast epithelial cells.
Baicalein has protective effects on the 17β-estradiol-induced transformation of breast epithelial cells.
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黄芩素对 17β-雌二醇诱导的乳腺上皮细胞转化有保护作用
DOI：
10.18632/oncotarget.14433
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发表时间：
2017-02-07
期刊：
影响因子：
--
通讯作者：
Shen XC
中科院分区：
文献类型：
--
作者：
Chen Y;Wang J;Hong DY;Chen L;Zhang YY;Xu YN;Pan D;Fu LY;Tao L;Luo H;Shen XC
流行病学和系统研究表明，类黄酮消费与乳腺癌的发病率较低有关。黄芩素（Baicalein）是从黄芩（Cordaria baicalensis Georgi）的根中提取的主要黄酮类化合物。本研究采用17β-雌二醇（17β-estradiol，E2）长期作用于乳腺上皮细胞，探讨黄芩素对乳腺癌细胞化学预防的作用。结果表明，黄芩素显着抑制E2诱导的细胞生长，运动和侵袭力，并抑制E2诱导的畸形腺泡形成在三维培养。此外，它抑制E2诱导的细胞在琼脂糖中形成克隆的能力和NOD/SCID免疫缺陷小鼠中的肿瘤。采用Sybyl-X 1.2软件进行对接研究，结果表明黄芩素可与雌激素受体α（ER α）和G蛋白偶联雌激素受体30（GPR 30）结合，这是E2介导的两条重要途径。黄芩素通过干扰ER α进入细胞核并随后与雌激素反应元件结合，从而降低ER α靶基因的mRNA水平，从而阻止E2诱导的ER α介导的细胞核转录信号的激活。它还抑制E2诱导的GPR 30介导的信号转导，以及GPR 30调节基因的转录。因此，这些结果表明，黄芩素是一种潜在的药物，用于降低雌激素依赖性乳腺癌的风险。
Epidemiologic and systematic studies have indicated that flavonoid consumption is associated with a lower incidence of breast cancer. Baicalein is the primary flavonoid derived from the roots of Scutellaria baicalensis Georgi. In the current study, the long-term exposure of breast epithelial cells to 17β-estradiol (E2) was used to investigate the chemopreventive potential of baicalein on neoplastic transformation. The results demonstrated that baicalein significantly inhibited E2-induced cell growth, motility, and invasiveness, and suppressed E2-induced misshapen acini formation in 3D cultures. Furthermore, it inhibited the ability of E2-induced cells to form clones in agarose and tumors in NOD/SCID immunodeficient mice. Docking studies using Sybyl-X 1.2 software showed that baicalein could bind to both estrogen receptor-α (ERa) and G-protein coupled estrogen receptor 30 (GPR30), which are two critical E2-mediated pathways. Baicalein prevented the E2-induced ERa-mediated activation of nuclear transcriptional signaling by interfering with the trafficking of ERa into the nucleus and subsequent binding to estrogen response elements, thereby decreasing the mRNA levels of ERa target genes. It also inhibited E2-induced GPR30-mediated signal transduction, as well as the transcription of GPR30-regulated genes. Therefore, these results suggest that baicalein is a potential drug for reducing the risk of estrogen-dependent breast cancer.