Laboratory of Pharmacology, Chulabhorn Research Institute, Bangkok, Thailand.
J Agric Food Chem. 2011 Jan 12;59(1):212-21. doi: 10.1021/jf102006w. Epub 2010 Dec 8.
Sesame lignans (sesamin, sesamolin) and their metabolites (enterodiol, ED; enterolactone, EL; and sesamol) have been evaluated for their estrogenic activities. ED and EL have been indicated to have estrogenic/antiestrogenic properties on human breast cancer cells; however the estrogenic activities of sesamin, sesamolin and sesamol have not been reported. In the present study, estrogenic potencies of sesame lignans and their metabolites were determined by estrogen responsive element (ERE) luciferase reporter assay in T47D cells stably transfected with ERE-luc (T47D-KBluc cells) and quantifying pS2 and progesterone receptor gene expression in T47D cells. All tested compounds except ED possessed ability of ERE activation with a very low potency compared to estradiol (E2). These effects were abolished by coincubating tested compounds with 1 μM ICI 182 780, suggesting that estrogen receptors were directly involved in their ERE activations. Among tested compounds, sesamol showed the highest ability in ERE induction. The coincubation of increasing concentration of E2 (10(-12)-10(-6) M) with 10 μM of tested compounds resulted in a downward shift of E2-ERE dose-response curves. In contrast, at the low concentration of E2 (10(-12) M), sesamin and sesamol significantly exhibited additive effects on the E2 responses. The inhibitory effect in a dose-dependent manner was also observed when 1-100 μM sesamol was coincubated with 1 nM E2. Sesamin, sesamol and EL significantly induced pS2 gene expression whereas only sesamol could significantly induce progesterone receptor gene. The data obtained in this study suggested that sesame lignans and their metabolites possess weak estrogenic/antiestrogenic activity.
芝麻木脂素（芝麻素、芝麻林素）及其代谢物（肠二醇、ED；肠内酯、EL；和芝麻酚）已被评估其雌激素活性。ED 和 EL 已被证明对人乳腺癌细胞具有雌激素/抗雌激素特性；然而，芝麻素、芝麻林素和芝麻酚的雌激素活性尚未报道。在本研究中，通过雌激素反应元件（ERE）荧光素酶报告基因分析在稳定转染 ERE-luc（T47D-KBluc 细胞）的 T47D 细胞中测定芝麻木脂素及其代谢物的雌激素效力，并在 T47D 细胞中定量测定 pS2 和孕激素受体基因表达。除 ED 外，所有测试化合物都具有激活 ERE 的能力，但其效力与雌二醇（E2）相比非常低。这些作用被与 1 μM ICI 182780 共孵育的测试化合物消除，表明雌激素受体直接参与其 ERE 激活。在测试的化合物中，芝麻酚显示出最强的 ERE 诱导能力。随着 E2 浓度（10-12-10-6 M）的增加，与 10 μM 测试化合物共孵育会导致 E2-ERE 剂量反应曲线向下移动。相比之下，在低浓度的 E2（10-12 M）下，芝麻素和芝麻酚在 E2 反应中显著表现出相加作用。当 1-100 μM 芝麻酚与 1 nM E2 共孵育时，也观察到剂量依赖性的抑制作用。芝麻素、芝麻酚和 EL 显著诱导 pS2 基因表达，而只有芝麻酚可以显著诱导孕激素受体基因。本研究获得的数据表明，芝麻木脂素及其代谢物具有较弱的雌激素/抗雌激素活性。
