早期研究十字花科類蔬菜提取物吲哚3 原醇（I3C）能抑制人雌激素依賴型乳腺癌細胞的增殖,，誘導雌激素受體α（ERα）蛋白的降解。
近日,，一項最新研究運用人乳腺癌MCF-7細胞開展相關(guān)研究,，發(fā)現(xiàn)I3C可降低胰島素樣生長因子受體1（IGF1R）和胰島素受體底物1（IRS1）的表達，抑制IGF1的下游信號轉(zhuǎn)導效應(yīng),。相關(guān)研究論文發(fā)表在Molecular and Cellular Endocrinology雜志上,。
加入外源性雌激素受體α能逆轉(zhuǎn)I3C介導的IGF1R和IRS1蛋白表達降低，這表明I3C可控制ERα下游調(diào)控的IGF1R和IRS1蛋白表達,。
I3C可破壞內(nèi)源性ERα的結(jié)合到IGF1R/IRS1 啟動子區(qū)域上的能力,，但不影響Sp1的結(jié)合力,。因此,，I3C可通過抑制ERα的轉(zhuǎn)錄，介導的細胞內(nèi)的IGF1級聯(lián)信號，抑制雌激素敏感的乳腺癌細胞增殖,?？傊甀3C是一個潛在的抗雌激素敏感的腫瘤治療藥物。（生物谷：Bioon.com）
編譯自：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
doi:10.1016/j.mce.2012.07.008
PMC:
PMID:
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
