The Flavonoid Apigenin Is a Progesterone Receptor Modulator with In Vivo Activity in the Uterus.
The Flavonoid Apigenin Is a Progesterone Receptor Modulator with In Vivo Activity in the Uterus.
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类黄酮替代蛋白是子宫内体内活性的孕酮受体调节剂。
DOI：
10.1007/s12672-018-0333-x
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发表时间：
2018-08
影响因子：
3
通讯作者：
Burdette JE
中科院分区：
文献类型：
--
作者：
Dean M;Austin J;Jinhong R;Johnson ME;Lantvit DD;Burdette JE
芹菜素是一种黄酮类化合物，具有良好的抗癌特性;然而，其作用机制仍不清楚。我们以前确定芹菜素作为一种潜在的植物生长素，一种天然产物与化学支架，与孕激素受体（PR）相互作用。我们的目的是通过分子对接研究，体外活性测定，芹菜素的能力，以确定芹菜素与PR相互作用的能力，并在体内引起孕激素样作用。分子对接证实，芹菜素可以与PR相互作用，但由于货车德瓦尔斯相互作用较少，亲和力低于孕酮。在稳定表达PR-B的石川细胞中，芹菜素在5和10 μM时显著增加孕酮反应元件/荧光素酶（PRE/Luc）活性，但在缺乏PR表达的亲本石川细胞中则没有。在存在100 nM孕酮的情况下，10 μM芹菜素降低PRE/Luc活性，表明混合激动剂活性。芹菜素还引发PR在石川PR-B细胞中的降解，如通过蛋白质印迹所测量的。芹菜素抑制石川细胞增殖，但通过PR独立的机制。相反，芹菜素和孕酮都刺激T47 D细胞的增殖，RU 486阻断了这种作用。芹菜素激活其他核受体，这通过在PR阴性的MDA-MB-231细胞中增加的荧光素酶活性来证明。在体内，芹菜素阻断了染料木素刺激的子宫上皮细胞高度的增加，刺激子宫内膜表达Hand 2，PR刺激的转录因子，并显着降低染料木素诱导的增殖。总之，芹菜素是一种具有混合激动剂活性的植物黄素，其通过阻碍雌激素受体介导的子宫增殖而在体内显示活性。
Apigenin is a flavonoid with well-documented anti-cancer properties; however, its mechanisms of action are still unclear. We previously identified apigenin as a potential phytoprogestin, a natural product with a chemical scaffold that interacts with the progesterone receptor (PR). Our objective was to characterize the ability of apigenin to interact with PR through molecular docking studies, in vitro activity assays, and the ability of apigenin to elicit progestin-like effects in vivo. Molecular docking confirmed that apigenin could interact with PR, though with lower affinity than progesterone due to fewer van der Waals interactions. In Ishikawa cells stably expressing PR-B, apigenin significantly increased progesterone response element/luciferase (PRE/Luc) activity at 5 and 10 μM, but not in the parental Ishikawa cells that lack PR expression. In the presence of 100 nM of progesterone, 10 μM apigenin reduced PRE/Luc activity, indicative of mixed agonist activity. Apigenin also triggered degradation of PR in Ishikawa PR-B cells as measured by western blot. Apigenin reduced proliferation of Ishikawa cells, but through a PR independent mechanism. In contrast, apigenin and progesterone both stimulated proliferation of T47D cells, an effect blocked by RU486. Apigenin activated other nuclear receptors evidenced by increased luciferase activity in MDA-MB-231 cells, which are PR negative. In vivo, apigenin blocked the genistein-stimulated increase in uterine epithelial cell height; stimulated endometrial expression of Hand2, a transcription factor stimulated by PR, and significantly reduced genistein-induced proliferation. In summary, apigenin is a phytoprogestin, with mixed agonist activity that demonstrates activity in vivo by hindering estrogen receptor mediated uterine proliferation.
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影响因子：
3.9
作者：
Choi, Jaesung (Peter);Desai, Reena;Simanainen, Ulla
通讯作者：
Simanainen, Ulla
类黄酮、类黄酮亚类和乳腺癌风险：流行病学研究的荟萃分析。
影响因子：
3.7
作者：
Hui C;Qi X;Qianyong Z;Xiaoli P;Jundong Z;Mantian M
通讯作者：
Mantian M
影响因子：
--
作者：
Cook MT;Liang Y;Besch-Williford C;Goyette S;Mafuvadze B;Hyder SM
通讯作者：
Hyder SM
DOI：
10.3945/ajcn.114.088708
发表时间：
2014-11
期刊：
The American journal of clinical nutrition
影响因子：
--
作者：
Cassidy A;Huang T;Rice MS;Rimm EB;Tworoger SS
通讯作者：
Tworoger SS
影响因子：
3.5
作者：
Diep CH;Daniel AR;Mauro LJ;Knutson TP;Lange CA
通讯作者：
Lange CA