Mol Cell Endocrinol：十字花科类蔬菜提取物吲哚3原醇抗乳腺癌细胞增殖机制

早期研究十字花科类蔬菜提取物吲哚3 原醇（I3C）能抑制人雌激素依赖型乳腺癌细胞的增殖，诱导雌激素受体α（ERα）蛋白的降解。

近日，一项最新研究运用人乳腺癌MCF-7细胞开展相关研究，发现I3C可降低胰岛素样生长因子受体1（IGF1R）和胰岛素受体底物1（IRS1）的表达，抑制IGF1的下游信号转导效应。相关研究论文发表在Molecular and Cellular Endocrinology杂志上。

加入外源性雌激素受体α能逆转I3C介导的IGF1R和IRS1蛋白表达降低，这表明I3C可控制ERα下游调控的IGF1R和IRS1蛋白表达。

I3C可破坏内源性ERα的结合到IGF1R/IRS1 启动子区域上的能力，但不影响Sp1的结合力。因此，I3C可通过抑制ERα的转录，介导的细胞内的IGF1级联信号，抑制雌激素敏感的乳腺癌细胞增殖。总之I3C是一个潜在的抗雌激素敏感的肿瘤治疗药物。

编译自：Indole-3-Carbinol disrupts estrogen receptor-alpha dependent expression of insulin-like growth factor-1 receptor and insulin receptor substrate-1 and proliferation of human breast cancer cells

原文摘要：

Indole-3-Carbinol disrupts estrogen receptor-alpha dependent expression of insulin-like growth factor-1 receptor and insulin receptor substrate-1 and proliferation of human breast cancer cells

Crystal N. Marconett, Ankur K. Singhal, Shyam N. Sundar, Gary L. Firestone

We previously established that Indole-3-Carbinol (I3C), a natural hydrolysis product of glucobrassicin in cruciferous vegetables, arrests the proliferation of estrogen-dependent human breast cancer cells and induces protein degradation of estrogen receptor-alpha (ERα). We demonstrate in human MCF-7 breast cancer cells that I3C ablates expression of Insulin-like Growth Factor Receptor-1 (IGF1R) and Insulin Receptor Substrate-1 (IRS1), downstream effectors of the IGF1 signaling pathway. Exogenous ERα reversed the I3C mediated loss of IGF1R and IRS1 gene expression demonstrating that down-regulation of ERα is functionally linked to I3C control of IGF1R and IRS1 expression. I3C disrupted binding of endogenous ERα, but not Sp1, to ERE-Sp1 composite elements within the IGF1R/IRS1 promoters. Exogenous ERα abrogated, and combined expression of IGF1R and IRS1 attenuated, the I3C mediated cell cycle arrest. Therefore, I3C inhibits proliferation of estrogen-sensitive breast cancer cells through disruption of ERα-mediated transcription of cell signaling components within the IGF1 cascade. Disruption of IGF1R and IRS1 expression is a new I3C anti-proliferative pathway. I3C arrests breast cancer cell proliferation by ablating IGF1R and IRS1 expression. I3C down-regulation of ERα triggers the loss of IGF1R and IRS1 gene expression. I3C disrupts the interactions of endogenous ERα with composite ERE-Sp1 DNA elements. I3C represents a potential anti-cancer therapeutic for estrogen sensitive cancers