Resveratrol exhibits cytostatic and antiestrogenic properties with human endometrial adenocarcinoma (Ishikawa) cells.
Resveratrol exhibits cytostatic and antiestrogenic properties with human endometrial adenocarcinoma (Ishikawa) cells.
复制标题
DOI：
--
复制
发表时间：
2001-08
期刊：
影响因子：
11.2
通讯作者：
Krishna P. L. Bhat;J. Pezzuto
中科院分区：
文献类型：
--
作者：
Krishna P. L. Bhat;J. Pezzuto
反式-3，4 '，5-三羟基芪（白藜芦醇）是一种存在于人类饮食中的多酚类化合物，最近报道了其作为一种雌激素激动剂与转染有雌激素反应元件-荧光素酶报告质粒的培养MCF-7细胞一起使用。如目前所示，白藜芦醇（浓度高达10 μ M）处理培养的人子宫内膜腺癌（石川）细胞，并没有显着增加雌激素诱导的标记酶，碱性磷酸酶的水平。相反，当用1 nM的17 β-雌二醇（E（2））诱导碱性磷酸酶时，白藜芦醇的活性表现出剂量依赖性降低（IC（50）= 2.3 μ M）。此外，当石川细胞用白藜芦醇作为单一药剂处理时，雌激素诱导的孕酮受体（PR）没有增强，并且白藜芦醇在mRNA和蛋白水平上以剂量依赖性方式抑制由E（2）处理诱导的PR表达。此外，白藜芦醇介导PR功能活性的抑制，如通过下调E（2）加孕酮诱导的α（1）-整联蛋白表达所证明的。用石川细胞进行瞬时转染实验，通过剂量依赖性抑制E（2）诱导的雌激素反应元件-荧光素酶转录活性证实了抗雌激素作用。由于白藜芦醇在石川细胞中拮抗雌激素效应，因此进行竞争结合分析以检查从人雌激素受体（ER）置换[（3）H]E（2）的潜力。白藜芦醇对ER-α没有明显的活性，但对ER-β，E（2）被取代，IC（50）为125 μ M。然而，在5-15 μ M的浓度范围内，白藜芦醇在石川细胞中抑制ER-α而不是ER-β的mRNA和蛋白质表达。此外，在存在或不存在E（2）的情况下，白藜芦醇以时间依赖性方式抑制石川细胞增殖，细胞在周期的S期累积≤ 48 h。这种影响是可逆的。一些关键的细胞周期蛋白的分析表明，细胞周期蛋白A和E的表达，但在细胞周期蛋白依赖性激酶2的减少的具体增加。这些数据表明，白藜芦醇在石川细胞中发挥抗增殖作用，这种作用可能是由雌激素依赖性和非依赖性机制介导的。
Trans-3,4',5-trihydroxystilbene (resveratrol), a polyphenolic compound found in the human diet, was reported recently to serve as an estrogen agonist with cultured MCF-7 cells transfected with estrogen response element-luciferase reporter plasmids. As currently shown, treatment of cultured human endometrial adenocarcinoma (Ishikawa) cells with resveratrol (concentrations as high as 10 microM) did not significantly increase the levels of an estrogen-inducible marker enzyme, alkaline phosphatase. To the contrary, when alkaline phosphatase was induced by treatment with 1 nM of 17beta-estradiol (E(2)), resveratrol exhibited a dose-dependent decrease in activity (IC(50) = 2.3 microM). Furthermore, when Ishikawa cells were treated with resveratrol as a single agent, estrogen-inducible progesterone receptor (PR) was not enhanced, and PR expression induced by treatment with E(2) was inhibited by resveratrol in a dose-dependent fashion at both the mRNA and protein levels. In addition, resveratrol mediated suppression of a functional activity of PR as demonstrated by down-regulation of alpha(1)-integrin expression induced by E(2) plus progesterone. With transient transfection experiments conducted with Ishikawa cells, antiestrogenic effects were confirmed by dose-dependent inhibition of E(2)-induced estrogen response element-luciferase transcriptional activity. Because resveratrol antagonized estrogenic effects in Ishikawa cells, competitive binding analyses were performed to examine the potential of displacing [(3)H]E(2) from human estrogen receptor (ER). Resveratrol showed no discernable activity with ER-alpha, but with ER-beta, E(2) was displaced with an IC(50) of 125 microM. However, mRNA and protein expression of ER-alpha but not ER-beta were suppressed by resveratrol in Ishikawa cells, in the concentration range of 5-15 microM. In addition, in the presence or absence of E(2), resveratrol inhibited Ishikawa cell proliferation in a time-dependent manner with cells accumulating in the S phase of the cycle < or =48 h. This effect was reversible. Analysis of some critical cell cycle proteins revealed a specific increase in expression of cyclins A and E but a decrease in cyclin-dependent kinase 2. These data suggest resveratrol exerts an antiproliferative effect in Ishikawa cells, and the effect may be mediated by both estrogen-dependent and -independent mechanisms.