Enterodiol and enterolactone, two major diet-derived polyphenol metabolites have different impact on ERα transcriptional activation in human breast cancer cells
Enterodiol and enterolactone, two major diet-derived polyphenol metabolites have different impact on ERα transcriptional activation in human breast cancer cells
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DOI：
10.1016/j.jsbmb.2008.03.032
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发表时间：
2008-05-01
影响因子：
4.1
通讯作者：
Potier, Mylene
中科院分区：
文献类型：
--
作者：
Carreau, Charlotte;Flouriot, Gilles;Potier, Mylene
木脂素是在哺乳动物肠道中代谢产生雌激素肠木脂素、肠二醇（ED）和肠内酯（EL）的植物化合物。由于雌激素与乳腺癌病因有关，肠木脂素可能会影响乳腺癌风险，但据我们所知，它们在人类中发挥雌激素和/或抗雌激素作用的机制仍不清楚。为了更好地了解食物中的雌激素化合物（例如肠木脂素）如何影响乳腺癌进展及其在激素依赖性疾病中干扰人类雌激素受体（ER）信号传导的机制，我们检查并比较了 ED、EL 和 17 β-雌二醇 (E2) 诱导 ER α 和 ER β 反式激活、调节 ER α 靶基因、发挥生长刺激或抗增殖作用的能力，最后通过作用于基质金属蛋白酶 (MMP)-2 和 -9 来调节 MCF-7 细胞迁移，浓度可通过富含木酚素的饮食实现。这项研究表明，肠木脂素在 ER α 和 ER β 反式激活方面表现出不同的特性。 ED（如 E2）通过反式激活功能 AF-1 和 AF-2 诱导 ER α 转录激活，而 EL 在诱导 AF-1 方面效率较低，主要通过 AF-2 发挥作用。此外，ED和EL以不同的方式调节ERαmRNA和蛋白质含量以及MCF-7细胞增殖和分泌MMP活性。肠木脂素是当今引起广泛关注的化合物，我们的研究结果有助于揭示其对 ER 的作用机制，强调木脂素的膳食负荷对于乳腺癌风险或化学预防因素与女性健康之间的平衡至关重要。 (c) 2008 Elsevier Ltd. 保留所有权利。
Lignans are plant compounds metabolized in the mammalian gut to produce the estrogenic enterolignans, enterodiol (ED) and enterolactone (EL). Because estrogens have been linked to breast cancer etiology, enterolignans could affect breast cancer risk, but to our knowledge, the mechanisms by which they exert their estrogenic and/or anti-estrogenic effects in humans are still unclear. To better understand how estrogenic compounds from the food, such as the enterolignans, might influence breast cancer progression and their mechanisms to interfere with human estrogen receptor (ER) signalling in hormone-dependant diseases, we examined and compared the ability of ED, EL and 17 beta-estradiol (E2) to induce the transactivation of ER alpha and ER beta, to modulate ER alpha target genes, to exert either growth stimulatory or anti-proliferative effects and finally to modulate MCF-7 cell migration by acting on matrix metalloproteases (MMP)-2 and -9, at concentrations that are achievable through a lignan-rich diet. This study indicates that enterolignans show distinct properties for transactivation of ER alpha and ER beta. ED, as E2, induces ER alpha transcriptional activation through transactivation functions AF-1 and AF-2, while EL is less efficient in inducing AF-1, acting predominantly through AF-2. Furthermore, ED and EL modulate ER alpha mRNA and protein contents as well as MCF-7 cell proliferation and secreted MMP activities in a different way. Enterolignans are compounds of wide interest nowadays and our results help to unveil their mechanisms of action on ER, emphasizing the fact that the dietary load in lignans could be of importance in the balance between being risk or chemopreventive factors for breast cancer and women's health. (c) 2008 Elsevier Ltd. All rights reserved.