Estrogenic effects of extracts from cabbage, fermented cabbage, and acidified brussels sprouts on growth and gene expression of estrogen-dependent human breast cancer (MCF-7) cells.
Estrogenic effects of extracts from cabbage, fermented cabbage, and acidified brussels sprouts on growth and gene expression of estrogen-dependent human breast cancer (MCF-7) cells.
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卷心菜、发酵卷心菜和酸化球芽甘蓝提取物对雌激素依赖性人乳腺癌 (MCF-7) 细胞生长和基因表达的雌激素作用。
DOI：
10.1021/jf000164z
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发表时间：
2000
影响因子：
6.1
通讯作者：
Helferich,WG
中科院分区：
文献类型：
--
作者：
Ju,YH;Carlson,KE;Sun,J;Pathak,D;Katzenellenbogen,BS;Katzenellenbogen,JA;Helferich,WG
以冷冻干燥甘蓝（FDC）、冷冻干燥发酵甘蓝（FDS）和酸化布鲁塞尔芽菜（ABS）为原料，采用乙酸乙酯极限萃取法制备十字花科蔬菜提取物。分析了这些提取物的雌激素和抗雌激素作用。为了鉴定提取物是否是可以作为激动剂或拮抗剂的潜在雌激素受体（ER）配体，使用竞争性放射结合测定法测量提取物对ER的结合亲和力。提取物与雌激素受体的结合亲和力较低，其相对结合亲和力为雌二醇> FDS > FDC > ABS。这些提取物在雌激素依赖性人乳腺癌（MCF-7）细胞中评价其雌激素和抗雌激素活性，使用增殖和雌激素响应性pS2基因表达的诱导作为终点，使用北方印迹分析。在低浓度（5 - 25 ng/mL）下，所有提取物均降低1 nM雌二醇诱导的MCF-7细胞增殖。25 ng/mL的提取物也抑制雌二醇诱导的pS2 mRNA表达。然而，在较高的提取物浓度（50 ng/mL-25 μg/mL）下，观察到MCF-7细胞的增殖增加。类似地，较高的提取物浓度（0.25 - 25 μg/mL）诱导了pS2基因的表达。纯雌激素拮抗剂ICI 182，780抑制提取物和雌二醇诱导的细胞增殖，也抑制提取物诱导的pS2表达。采用人子宫内膜腺癌（HEC-1）细胞转染实验，分析FDC和FDS的ER亚型选择活性。FDS作为ERα选择性激动剂，而FDC完全激活ER-α和ER-β。ER阴性MDA-231细胞的生长不受提取物或雌二醇的影响。本研究表明，十字花科蔬菜提取物具有双功能，在低浓度下是抗雌激素，在高浓度下是雌激素激动剂.关键词：MCF-7;植物雌激素;甘蓝;发酵甘蓝; pS2基因; ERα; ERβ
Cruciferous vegetable extracts from freeze-dried cabbage (FDC), freeze-dried fermented cabbage (FDS), and acidified Brussels sprouts (ABS) were prepared by exhaustive extraction with ethyl acetate. Estrogenic and antiestrogenic effects of these extracts were analyzed. To identify whether the extracts are potential estrogen receptor (ER) ligands that can act as agonists or antagonists, the binding affinity of extracts for the ER was measured using a competitive radiometric binding assay. The extracts bound with low affinity to the ER, and the relative binding affinity is estradiol > FDS > FDC > ABS. These extracts were evaluated for their estrogenic and antiestrogenic activities in estrogen-dependent human breast cancer (MCF-7) cells using as endpoints proliferation and induction of estrogen-responsive pS2 gene expression, which was analyzed using Northern blot assay. At low concentrations (5−25 ng/mL) all of the extracts reduced 1 nM estradiol-induced MCF-7 cell proliferation. Extracts at 25 ng/mL also inhibited estradiol-induced pS2 mRNA expression. At higher extract concentrations (50 ng/mL−25 μg/mL), however, increased proliferation in MCF-7 cells was observed. Similarly, expression of the pS2 gene was induced by higher extract concentrations (0.25−25 μg/mL). The pure estrogen antagonist, ICI 182,780, suppressed the cell proliferation induced by the extracts as well as by estradiol and also the induction of pS2 expression by the extracts. The ER subtype-selective activities of FDC and FDS were analyzed using a transfection assay in human endometrial adenocarcinoma (HEC-1) cells. FDS acted as an ERα-selective agonist while FDC fully activated both ER-α and ER-β. Growth of the ER-negative MDA-231 cells was not affected by the extracts or by estradiol. This study demonstrates that cruciferous vegetable extracts act bifunctionally, like an antiestrogen at low concentrations and an estrogen agonist at high concentrations.Keywords: MCF-7; phytoestrogen; cabbage; fermented cabbage; pS2 gene; ERα; ERβ