Inhibitory Effect of Luteolin on Estrogen Biosynthesis in Human Ovarian Granulosa Cells by Suppression of Aromatase (CYP19)
Inhibitory Effect of Luteolin on Estrogen Biosynthesis in Human Ovarian Granulosa Cells by Suppression of Aromatase (CYP19)
复制标题
木犀草素通过抑制芳香酶（CYP19）对人卵巢颗粒细胞雌激素生物合成的抑制作用
DOI：
10.1021/jf3022817
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发表时间：
2012-08-29
影响因子：
6.1
通讯作者：
Zhang, Guo-lin
中科院分区：
文献类型：
--
作者：
Lu, Dan-feng;Yang, Li-juan;Zhang, Guo-lin
芳香化酶是雌激素生物合成的关键酶，抑制芳香化酶是治疗乳腺癌的重要策略。一些膳食黄酮类化合物显示出芳香化酶抑制活性，但其组织特异性和机制尚不清楚。这项研究发现，膳食黄酮类木犀草素以剂量和时间依赖性方式有效抑制来自人卵巢颗粒细胞的KGN细胞中雌激素的生物合成，而卵巢颗粒细胞是绝经前妇女雌激素的主要来源。木犀草素降低KGN细胞芳香化酶mRNA和蛋白表达。Luteolin也得到了提升。芳香酶蛋白降解和抑制雌激素的合成在芳香酶表达HEK293A细胞，但没有影响：重组：表达芳香酶。雌激素在KGN细胞的生物合成抑制不同的效力，洋葱和鸟辣椒提取物和其他四种膳食黄酮类化合物：山奈酚，槲皮素，杨梅素，异鼠李素。目前的研究表明，毛地黄黄酮抑制雌激素的生物合成，减少芳香化酶的表达和不稳定的芳香化酶蛋白，它值得进一步调查作为一个潜在的治疗雌激素依赖性癌症。
Inhibition of aromatase, the key enzyme in estrogen biosynthesis, is an important strategy in the treatment of breast cancer. Several dietary flavonoids show aromatase inhibitory activity, but their tissue specificity and mechanism remain unclear. This study found that the dietary flavonoid luteolin potently inhibited estrogen biosynthesis in a dose- and time-dependent manner in KGN cells derived from human ovarian granulosa Cells, the major source of estrogens in premenopausal, women. Luteolin decreased aromatase mRNA and protein expression in KGN cells. Luteolin also promoted. aromatase protein degradation and inhibited estrogen biosynthesis in aromatase-expressing HEK293A cells, but had no effect on :recombinant: expressed aromatase. Estrogen biosynthesis in KGN cells was inhibited with differing potencies by extracts of onion and bird chili and by four other-dietary flavonoids: kaempferol, quercetin, myricetin, and isorhamnetin. The present study suggests that luteolin inhibits estrogen biosynthesis by decreasing aromatase expression and destabilizing aromatase protein, and it warrants further investigation as a potential treatment for estrogen-dependent cancers.