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麦角甾烷-22-烯-3β-醇(3,5,22)通过 MCF-7 细胞中雌激素受体α依赖性信号通路的雌激素活性。

Estrogenic Activity of Mycoestrogen (3,5,22)-Ergost-22-en-3-ol via Estrogen Receptor α-Dependent Signaling Pathways in MCF-7 Cells.

机构信息

College of Korean Medicine, Gachon University, Seongnam 13120, Korea.

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.

出版信息

Molecules. 2021 Dec 22;27(1):36. doi: 10.3390/molecules27010036.

DOI:10.3390/molecules27010036
PMID:35011267
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8746416/
Abstract

(Scop.) Sing., a mushroom of the family , has been used in traditional oriental medicine to treat cholecystitis, improve bile secretion, and regulate bile-duct pressure. The present study evaluated the estrogen-like effects of using a cell-proliferation assay in an estrogen-receptor-positive breast cancer cell line (MCF-7). We found that the methanol extract of fruiting bodies promoted cell proliferation in MCF-7 cells. Using bioassay-guided fractionation of the methanol extract and chemical investigation, we isolated and identified four steroids and four fatty acids from the active fraction. All eight compounds were evaluated by E-screen assay for their estrogen-like effects in MCF-7 cells. Among the tested isolates, only (3,5,22)-ergost-22-en-3-ol promoted cell proliferation in MCF-7 cells; this effect was mitigated by the ER antagonist, ICI 182,780. The mechanism underlying the estrogen-like effect of (3,5,22)-ergost-22-en-3-ol was evaluated using Western blot analysis to detect the expression of extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), Akt, and estrogen receptor α (ERα). We found that (3,5,22)-ergost-22-en-3-ol induced an increase in phosphorylation of ERK, PI3K, Akt, and ERα. Together, these experimental results suggest that (3,5,22)-ergost-22-en-3-ol is responsible for the estrogen-like effects of and may potentially aid control of estrogenic activity in menopause.

摘要

(Scop.)Sing.,一种属于 的蘑菇,已在传统东方医学中用于治疗胆囊炎,促进胆汁分泌和调节胆管压力。本研究使用雌激素受体阳性乳腺癌细胞系(MCF-7)中的细胞增殖测定法评估了 的雌激素样作用。我们发现 子实体的甲醇提取物可促进 MCF-7 细胞的增殖。通过对甲醇提取物进行基于生物测定的分级分离和化学研究,我们从活性部分分离并鉴定了四种甾体和四种脂肪酸。所有八种化合物均通过 E-screen assay 在 MCF-7 细胞中评估其雌激素样作用。在所测试的分离物中,只有(3,5,22)-麦角甾-22-烯-3-醇可促进 MCF-7 细胞的增殖;这种作用被 ER 拮抗剂 ICI 182,780 减轻。通过 Western blot 分析评估了(3,5,22)-麦角甾-22-烯-3-醇的雌激素样作用的机制,以检测细胞外信号调节激酶(ERK),磷酸肌醇 3-激酶(PI3K),Akt 和雌激素受体α(ERα)的表达。我们发现(3,5,22)-麦角甾-22-烯-3-醇诱导 ERK,PI3K,Akt 和 ERα 的磷酸化增加。综上所述,这些实验结果表明(3,5,22)-麦角甾-22-烯-3-醇是 的雌激素样作用的原因,并可能有助于控制更年期的雌激素活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9b/8746416/bcd6dfd14596/molecules-27-00036-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9b/8746416/b84198b5cb24/molecules-27-00036-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9b/8746416/cb620919ae32/molecules-27-00036-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9b/8746416/a72e19866122/molecules-27-00036-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9b/8746416/50c15b531ea4/molecules-27-00036-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9b/8746416/4b2e1f27e73f/molecules-27-00036-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9b/8746416/264df464e49b/molecules-27-00036-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9b/8746416/5989fa2c27e8/molecules-27-00036-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9b/8746416/bcd6dfd14596/molecules-27-00036-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9b/8746416/b84198b5cb24/molecules-27-00036-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9b/8746416/cb620919ae32/molecules-27-00036-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9b/8746416/a72e19866122/molecules-27-00036-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9b/8746416/50c15b531ea4/molecules-27-00036-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9b/8746416/4b2e1f27e73f/molecules-27-00036-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9b/8746416/264df464e49b/molecules-27-00036-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9b/8746416/5989fa2c27e8/molecules-27-00036-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9b/8746416/bcd6dfd14596/molecules-27-00036-g008.jpg

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