Mammalian lignans and genistein decrease the activities of aromatase and 17β-hydroxy steroid dehydrogenase in MCF-7 cells
Mammalian lignans and genistein decrease the activities of aromatase and 17β-hydroxy steroid dehydrogenase in MCF-7 cells
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DOI：
10.1016/j.jsbmb.2005.02.002
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发表时间：
2005-04-01
影响因子：
4.1
通讯作者：
Thompson, LU
中科院分区：
文献类型：
--
作者：
Brooks, JD;Thompson, LU
雌激素在乳腺癌的发生和发展中起着重要作用。乳腺组织和细胞系含有雌激素合成所必需的酶，包括芳香酶和17 β-羟基类固醇脱氢酶（17 β-HSD）。这些酶可以影响组织暴露于雌激素，因此已成为乳腺癌治疗和预防的目标。本研究确定了木脂素（GEN）和哺乳动物木脂素肠内酯（EL）和肠二醇（艾德）是否会抑制MCF-7癌细胞中芳香化酶和17 β-HSD I型的活性，从而降低雌二醇（E2）的产生量，从而降低细胞增殖。结果显示，10 μ M的EL、艾德和GEN显著降低了通过芳香酶途径产生的雌酮（El）的量，分别降低了37%、81%和70%。关于17 β-HSD 1型，50 μ M EL和GEN分别最大抑制E2产生84%和59%。通过EL的El和E2产生的减少和通过GEN的E2产生的减少与MCF-7细胞增殖的减少显著相关。4-羟基雄甾烯-3，17-二酮（50 μ M）不抑制芳香酶，但抑制E1向E2的转化达78%，表明它是17 β-HSD 1型抑制剂。总之，局部E2合成的调节是艾德、EL和GEN可能保护乳腺癌的一个潜在机制。(c)2005爱思唯尔有限公司保留所有权利。
Estrogen plays a major role in breast cancer development and progression. Breast tissue and cell lines contain the necessary enzymes for estrogen synthesis, including aromatase and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD). These enzymes can influence tissue exposure to estrogen and therefore have become targets for breast cancer treatment and prevention. This study determined whether the isoflavone genistein (GEN) and the mammalian lignans enterolactone (EL) and enterodiol (ED) would inhibit the activity of aromatase and 17 beta-HSD type I in MCF-7 cancer cells, thereby decreasing the amount of estradiol (E2) produced and consequently cell proliferation. Results showed that 10 mu M EL, ED and GEN significantly decreased the amount of estrone (El) produced via the aromatase pathway by 37 %, 81 % and 70 %, respectively. Regarding 17 beta-HSD type 1, 50 mu M EL and GEN maximally inhibited E2 production by 84 % and 59 %, respectively. The reduction in El and E2 production by EL and the reduction in E2 production by GEN were significantly related to a reduction in MCF-7 cell proliferation. 4-Hydroxyandrostene-3,17-dione (50 mu M) did not inhibit aromatase but inhibited the conversion of El to E2 by 78 %, suggesting that it is a 17 beta-HSD type 1 inhibitor. In conclusion, modulation of local E2 synthesis is one potential mechanism through which ED, EL and GEN may protect against breast cancer. (c) 2005 Elsevier Ltd. All rights reserved.