Inhibition of estrogen receptor alpha expression and function in MCF-7 cells by kaempferol
Inhibition of estrogen receptor alpha expression and function in MCF-7 cells by kaempferol
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DOI：
10.1002/jcp.10398
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发表时间：
2004-02-01
影响因子：
5.6
通讯作者：
Hung, H
中科院分区：
文献类型：
--
作者：
Hung, H
雌激素对雌激素受体（ER）阳性乳腺癌细胞具有促有丝分裂作用。目前ER阳性乳腺肿瘤的治疗旨在阻断雌激素活性。我们报告用山奈酚治疗 ER 阳性乳腺癌细胞导致细胞数量呈时间和剂量依赖性减少。对于 ER 阳性和 ER 阴性乳腺癌细胞，在 48 小时产生 50% 生长抑制所需的浓度分别约为 35.0 和 70.0 μM。对于MCF-7细胞，用17.5、35.0和70.0μM山奈酚处理24小时后，观察到ER-α mRNA的减少分别相当于对照的50%、12%、10%。与此同时，这些治疗导致 ER-α 蛋白减少 58%、80% 和 85%。山奈酚对 ER-α 水平的抑制作用早在治疗后 6 小时就可见。山奈酚治疗还导致孕酮受体 (PgR)、细胞周期蛋白 D1 和胰岛素受体底物 1 (IRS-1) 的表达出现剂量依赖性下降。免疫细胞化学研究表明，山奈酚处理的 MCF-7 细胞中的 ER-α 蛋白在细胞核中形成聚集。山奈酚还通过与抗雌激素 ICI 182,780 和雌二醇不同的途径诱导 ER-α 降解。在用山奈酚共同处理的细胞中，雌二醇诱导的 MCF-7 细胞增殖和雌激素响应元件报告基因活性的表达被消除。这些发现表明，山奈酚对 ER-α 表达和功能的调节可能部分是其在体外观察到的抗增殖作用的原因。 (C) 2003 Wiley-Liss, Inc.
Estrogens are mitogenic for estrogen receptor (ER)-positive breast cancer cells. Current treatment of ER-positive breast tumors is directed towards interruption of estrogen activity. We report that treatment of ER-positive breast cancer cells with kaempferol resulted in a time- and dose-dependent decrease in cell number. The concentration required to produce 50% growth inhibition at 48 h was approximately 35.0 and 70.0 muM for ER-positive and ER-negative breast cancer cells, respectively. For MCF-7 cells, a reduction in the ER-alpha mRNA equivalent to 50, 12, 10% of controls was observed 24 h after treatment with 17.5, 35.0, and 70.0 muM of kaempferol, respectively. Concomitantly, these treatments led to a 58, 80, and 85% decrease in ER-alpha protein. The inhibitory effect of kaempferol on ER-alpha levels was seen as early as 6 h post-treatment. Kaempferol treatment also led in a dose-dependent decrease in the expression of progesterone receptor (PgR), cyclin D1, and insulin receptor substrate 1 (IRS-1). Immunocytochemical study revealed that ER-alpha protein in kaempferol-treated MCF-7 cells formed an aggregation in the nuclei. Kaempferol also induced degradation of ER-alpha by a different pathway than that were observed for the antiestrogen ICI 182,780 and estradiol. Estradiol-induced MCF-7 cell proliferation and expression of the estrogen-responsive-element-reporter gene activity were abolished in cells co-treated with kaempferol. These findings suggest that modulation of ER-alpha expression and function by kaempferol may be, in part, responsible for its anti-proliferative effects seen in in vitro. (C) 2003 Wiley-Liss, Inc.