Lu R, Serrero G
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore 21201, USA.
J Cell Physiol. 1999 Jun;179(3):297-304. doi: 10.1002/(SICI)1097-4652(199906)179:3<297::AID-JCP7>3.0.CO;2-P.
Resveratrol is a natural phytoalexin compound found in grapes and other food products. In this study, the effect of resveratrol on the growth of human breast cancer cells was examined. Results show that resveratrol inhibits the growth of estrogen receptor(ER)-positive MCF-7 cells in a dose-dependent fashion. Detailed studies with MCF-7 cells demonstrate that resveratrol antagonized the growth-promoting effect of 17-beta-estradiol (E2) in a dose-dependent fashion at both the cellular (cell growth) and the molecular (gene activation) levels. At 5 x 10(-6) M, resveratrol abolished the growth-stimulatory effect mediated by concentrations of E2 up to 10(-9) M. The antiestrogenic effect of resveratrol could be observed at a concentration of 10(-6) M and above. The antiestrogenic effect of resveratrol was also demonstrated at the molecular level. Resveratrol in a dose-dependent fashion antagonized the stimulation by E2 of progesterone receptor gene expression in MCF-7 cells. Moreover, expression of transforming growth factor-alpha and insulin-like growth factor I receptor mRNA was inhibited while the expression of transforming growth factor beta2 mRNA was significantly elevated in MCF-7 cells cultivated in the presence of resveratrol (10(-5) M). In summary, our results show that resveratrol, a partial ER agonist itself, acts as an ER antagonist in the presence of estrogen leading to inhibition of human breast cancer cells.
白藜芦醇是一种存在于葡萄和其他食品中的天然植物抗毒素化合物。在本研究中，检测了白藜芦醇对人乳腺癌细胞生长的影响。结果表明，白藜芦醇以剂量依赖的方式抑制雌激素受体（ER）阳性的MCF - 7细胞的生长。对MCF - 7细胞的详细研究表明，白藜芦醇在细胞（细胞生长）和分子（基因激活）水平上均以剂量依赖的方式拮抗17 - β - 雌二醇（E2）的促生长作用。在5×10⁻⁶ M时，白藜芦醇消除了浓度高达10⁻⁹ M的E2介导的生长刺激作用。在10⁻⁶ M及以上浓度可观察到白藜芦醇的抗雌激素作用。白藜芦醇的抗雌激素作用在分子水平上也得到了证实。白藜芦醇以剂量依赖的方式拮抗E2对MCF - 7细胞中孕激素受体基因表达的刺激。此外，在存在白藜芦醇（10⁻⁵ M）培养的MCF - 7细胞中，转化生长因子 - α和胰岛素样生长因子I受体mRNA的表达受到抑制，而转化生长因子β2 mRNA的表达显著升高。总之，我们的结果表明，白藜芦醇本身作为一种部分ER激动剂，在雌激素存在的情况下作为ER拮抗剂，导致人乳腺癌细胞受到抑制。
