Estrogenic and antiproliferative properties of genistein and other flavonoids in human breast cancer cells in vitro
Estrogenic and antiproliferative properties of genistein and other flavonoids in human breast cancer cells in vitro
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DOI：
10.1080/01635589709514498
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发表时间：
1997-01-01
影响因子：
2.9
通讯作者：
Duwe, G
中科院分区：
文献类型：
--
作者：
Zava, DT;Duwe, G
实验和流行病学研究支持大豆食品预防癌症以及与雌激素缺乏相关的疾病和症状的观点。最近的研究表明，异黄酮金雀异黄酮（一种在大豆食品中含量丰富的植物雌激素）可能是带来这些健康益处的主要分子成分之一。在这项研究中，我们研究了广泛的生理相关浓度范围的金雀异黄酮对体外生长的 ER(+) 和 ER(-) 人乳腺癌细胞中雌激素受体 (ER) 结合、雌激素调节抗原 pS2 的诱导以及细胞增殖率的影响。将金雀异黄酮的剂量反应与雌二醇、他莫昔芬和其他几种结构相似的异类黄酮和生物类黄酮（例如雌马酚、山奈酚和槲皮素）的剂量反应进行了比较。我们的结果表明，金雀异黄素在生理可达到的浓度范围（10 nM-20 mu M）内具有有效的雌激素激动剂和细胞生长抑制作用。相同浓度范围内的其他类黄酮是良好的雌激素激动剂和较差的细胞生长抑制剂（雌马酚）或较差的雌激素激动剂和有效的生长抑制剂（山奈酚和槲皮素）。黄酮类化合物的生长抑制作用与三苯基抗雌激素如他莫昔芬的作用明显不同。总之，我们的结果表明金雀异黄酮在所测试的类黄酮中是独一无二的，因为它在生理相关浓度范围内具有有效的雌激素激动剂和细胞生长抑制作用。
Experimental and epidemiologic studies support the view that soyfoods prevent cancer as well as diseases and symptoms associated with estrogen deficiency. Recent research suggests that the isoflavonoid genistein, a phytoestrogen found in abundance in soyfoods, may be one of the principal molecular components responsible for these health benefits. In this study we investigated the effects of a broad physiologically relevant concentration range of genistein on estrogen receptor (ER) binding, induction of the estrogen-regulated antigen pS2, and cell proliferation rate in ER(+) and ER(-) human breast cancer cells grown in vitro. Dose response to genistein was compared with that of estradiol, tamoxifen, and several other structurally similar iso- and bioflavonoids (e.g., equol, kaempferol, and quercetin). Our results revealed that genistein has potent estrogen agonist and cell growth-inhibitory actions over a physiologically achievable concentration range (10 nM-20 mu M). Other flavonoids over the same concentration range were good estrogen agonists and poor cell growth inhibitors (equol) or poor estrogen agonists and potent growth inhibitors (kaempferol and quercetin). The growth-inhibitory actions of flavonoids were distinctly different from those of triphenyl antiestrogens like tamoxifen. In summary, our results reveal that genistein is unique among the flavonoids tested, in that if has potent estrogen agonist and cell growth-inhibitory actions over a physiologically relevant concentration range.