Two natural products, trans-phytol and (22E)-ergosta-6,9,22-triene-3 beta,5 alpha,8 alpha-triol, inhibit the biosynthesis of estrogen in human ovarian granulosa cells by aromatase (CYP19)
文献类型：期刊论文
| 作者 | Guo, Jiajia ; Yuan, Yun ; Lu, Danfeng ; Du, Baowen ; Xiong, Liang ; Shi, Jiangong ; Yang, Lijuan ; Liu, Wanli ; Yuan, Xiaohong ; Zhang, Guolin ; Wang, Fei |
| 刊名 | TOXICOLOGY AND APPLIED PHARMACOLOGY
 |
| 出版日期 | 2014 |
| 卷号 | 279期号:1页码:23-32 |
| 关键词 | Aromatase Granulosa cells Estrogen biosynthesis Phytol Ergosta-6 p38 MAPK 9 22-triene-3 beta 5 alpha 8 alpha-triol |
| 产权排序 | 1 |
| 通讯作者 | Zhang, GL (reprint author), Chinese Acad Sci, Chengdu Inst Biol, PO 416, Chengdu 610041, Peoples R China. |
| 合作状况 | 其它 |
| 英文摘要 | Aromatase is the only enzyme in vertebrates to catalyze the biosynthesis of estrogens. Although inhibitors of aromatase have been developed for the treatment of estrogen-dependent breast cancer, the whole-body inhibition of aromatase causes severe adverse effects. Thus, tissue-selective aromatase inhibitors are important for the treatment of estrogen-dependent cancers. In this study, 63 natural products with diverse structures were examined for their effects on estrogen biosynthesis in human ovarian granulosa-like KGN cells. Two compounds trans-phytol (SA-20) and (22E)-ergosta-6,9,22-triene-3 beta,5 alpha,8 alpha-triol (SA-48)-were found to potently inhibit estrogen biosynthesis (IC50: 1 mu M and 0.5 mu M, respectively). Both compounds decreased aromatase mRNA and protein expression levels in KGN cells, but had no effect on the aromatase catalytic activity in aromatase-overexpressing HEK293A cells and recombinant expressed aromatase. The two compounds decreased the expression of aromatase promoter I.3/II. Neither compound affected intracellular cyclic AMP (cAMP) levels, but they inhibited the phosphorylation or protein expression of cAMP response element-binding protein (CREB). The effects of these two compounds on extracellular regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (MAPKs), and AKT/phosphoinositide 3-kinase (PI3K) pathway were examined. Inhibition of p38 MAPK could be the mechanism underpinning the actions of these compounds. Our results suggests that natural products structurally similar to SA-20 and SA-48 may be a new source of tissue-selective aromatase modulators, and that p38 MAPK is important in the basal control of aromatase in ovarian granulosa cells. SA-20 and SA-48 warrant further investigation as new pharmaceutical tools for the prevention and treatment of estrogen-dependent cancers. (C) 2014 Elsevier Inc. All rights reserved. |
| 学科主题 | Pharmacology & Pharmacy; Toxicology |
| 收录类别 | SCI |
| 语种 | 英语 |
| 公开日期 | 2016-02-26 |
| 源URL | [http://210.75.237.14/handle/351003/26671]  |
| 专题 | 成都生物研究所_天然产物研究 |
| 推荐引用方式 GB/T 7714 | Guo, Jiajia,Yuan, Yun,Lu, Danfeng,et al. Two natural products, trans-phytol and (22E)-ergosta-6,9,22-triene-3 beta,5 alpha,8 alpha-triol, inhibit the biosynthesis of estrogen in human ovarian granulosa cells by aromatase (CYP19)[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,2014,279(1):23-32. |
| APA | Guo, Jiajia.,Yuan, Yun.,Lu, Danfeng.,Du, Baowen.,Xiong, Liang.,...&Wang, Fei.(2014).Two natural products, trans-phytol and (22E)-ergosta-6,9,22-triene-3 beta,5 alpha,8 alpha-triol, inhibit the biosynthesis of estrogen in human ovarian granulosa cells by aromatase (CYP19).TOXICOLOGY AND APPLIED PHARMACOLOGY,279(1),23-32. |
| MLA | Guo, Jiajia,et al."Two natural products, trans-phytol and (22E)-ergosta-6,9,22-triene-3 beta,5 alpha,8 alpha-triol, inhibit the biosynthesis of estrogen in human ovarian granulosa cells by aromatase (CYP19)".TOXICOLOGY AND APPLIED PHARMACOLOGY 279.1(2014):23-32. |
入库方式： OAI收割
来源：成都生物研究所
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