title: Evaluation of estrogenic/antiestrogenic activity of ellagic acid via the estrogen receptor subtypes ERalpha and ERbeta.
abstract: 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 ERalpha and ERbeta in HeLa cells. Cells co-transfected with an estrogen response element (ERE)-driven luciferase (Luc) reporter gene and an ERalpha- or ERbeta-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 ERalpha, whereas it was a complete estrogen antagonist via ERbeta. Further evaluation revealed that ellagic acid was a potent antiestrogen in MCF-7 breast cancer-derived cells, increasing, like the pure estrogen antagonist ICI182780, 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).
authors.affiliation: Department of Biological Chemistry, Medical School, University of Athens Mikras Asias Str 75, Goudi, Athens 11527, Greece.
authors.forename: Zoi
authors.initials: Z
authors.lastname: Papoutsi
authors.forename: Eva
authors.initials: E
authors.lastname: Kassi
authors.forename: Anna
authors.initials: A
authors.lastname: Tsiapara
authors.forename: Nikolas
authors.initials: N
authors.lastname: Fokialakis
authors.forename: George P
authors.initials: GP
authors.lastname: Chrousos
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Moutsatsou
mesh_terms: D001943:Breast Neoplasms; D002113:Calcification, Physiologic / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D004610:Ellagic Acid / Q000494:pharmacology*; D016889:Endometrial Neoplasms; D004965:Estrogen Antagonists / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D047629:Estrogen Receptor beta / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D010006:Osteoblasts; D014162:Transfection
chemical_list: D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D004610:Ellagic Acid