Evaluation of estrogenic/antiestrogenic activity of ellagic acid via the estrogen receptor subtypes ERα and ERβ

被引:85
|
作者
Papoutsi, Z
Kassi, E
Tsiapara, A
Fokialakis, N
Chrousos, GP
Moutsatsou, P
机构
[1] Univ Athens, Sch Med, Dept Biol Chem, Athens 11527, Greece
[2] Univ Athens, Dept Pharm, Dept Pharmacognosy, Athens 15771, Greece
[3] Univ Athens, Agia Sophia Childrens Hosp, Sch Med, A Dept Pediat, Athens 11527, Greece
关键词
ellagic acid; estrogen receptor alpha; estrogen receptor beta; selective estrogen receptor modulator; osteoblasts;
D O I
10.1021/jf0510539
中图分类号
S [农业科学];
学科分类号
09 ;
摘要
Ellagic acid is a plant-derived polyphenol, possessing antioxidant, antiproliferative, and antiatherogenic properties. Whether this compound has estrogenic/antiestrogenic activity, however, remains largely unknown. To answer this question, we first investigated the ability of ellagic acid to influence the activity of the estrogen receptor subtypes ER alpha and E beta in HeLa cells. Cells co-transfected with an estrogen response element (ERE)-driven luciferase (Luc) reporter gene and an ER alpha- or ER beta-expression vector were exposed to graded concentrations of ellagic acid. At low concentrations (10(-7) to 10(-9) M), this compound displayed a small but significant estrogenic activity via ER alpha, whereas it was a complete estrogen antagonist via ER. Further evaluation revealed that ellagic acid was a potent antiestrogen in MCF-7 breast cancer-derived cells, increasing, like the pure estrogen antagonist ICl182780, IGFBP-3 levels. Moreover, ellagic acid induced nodule mineralization in an osteoblastic cell line (KS483), an effect that was abolished by the estrogen antagonist. Endometrium-derived epithelial cells (Ishikawa) showed no response to the natural compound by using a cell viability assay (MTT). These findings suggest that ellagic acid may be a natural selective estrogen receptor modulator (SERM).
引用
收藏
页码:7715 / 7720
页数:6
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