title: Estrogenic activity of isoflavonoids from Onobrychis ebenoides.
abstract: Fractionation of the neutral extract of Onobrychis ebenoides (Leguminosae) yielded a new isoflavone, named ebenosin (1), in addition to the known ones, afrormosin (2), formononetin (3) and daidzein (4). Although the relative binding affinities of 1 - 4 for estrogen receptor alpha (ERalpha) were nearly comparable and matched those of 1-3 for ERbeta, that of 4 for the latter receptor was significantly higher than any of the other. Compounds 1 - 4 induced cell proliferation and gene expression in breast and endometrial cancer cells in an ER-dependent manner. Nonetheless, the rank order of induction potencies ( 4 > 3 >or= 2 >or= 1) matched better that of affinities for ERbeta ( 4 > 3 >or= 2 >or= 1) rather than ERalpha ( 4 >or= 3 >or= 2 >or= 1). While the antiestrogen ICI 182,780 could inhibit the induction of proliferation of ER-positive breast cancer cells by 1-4, it could not prevent 1 from exhibiting significant ER-independent cytotoxicity at 10 microM. By contrast, 1 was much less cytotoxic and only weakly estrogenic for ER-positive endometrial adenocarcinoma cells. In conclusion, our data suggest that the C-8 isoprenyl substituent of 1 renders it cytotoxic and/or estrogenic in a cell-dependent manner.
authors.affiliation: Division of Pharmacognosy and Natural Products Chemistry, School of Pharmacy, University of Athens, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Halabalaki
authors.forename: Xanthippi
authors.initials: X
authors.lastname: Alexi
authors.forename: Nektarios
authors.initials: N
authors.lastname: Aligiannis
authors.forename: George
authors.initials: G
authors.lastname: Lambrinidis
authors.forename: Harris
authors.initials: H
authors.lastname: Pratsinis
authors.forename: Ida
authors.initials: I
authors.lastname: Florentin
authors.forename: Sofia
authors.initials: S
authors.lastname: Mitakou
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mikros
authors.forename: Alexios-Leandros
authors.initials: AL
authors.lastname: Skaltsounis
authors.forename: Michael N
authors.initials: MN
authors.lastname: Alexis
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D007887:Fabaceae; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology; D048789:Phytoestrogens / Q000737:chemistry / Q000494:pharmacology*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D047628:Estrogen Receptor alpha; D007529:Isoflavones; D048789:Phytoestrogens; D010936:Plant Extracts