Estrogenic activity of isoflavonoids from Onobrychis ebenoides.
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.
Halabalaki
Maria
M
Division of Pharmacognosy and Natural Products Chemistry, School of Pharmacy, University of Athens, Athens, Greece.
Alexi
Xanthippi
X
Aligiannis
Nektarios
N
Lambrinidis
George
G
Pratsinis
Harris
H
Florentin
Ida
I
Mitakou
Sofia
S
Mikros
Emmanuel
E
Skaltsounis
Alexios-Leandros
AL
Alexis
Michael N
MN
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
D047628:Estrogen Receptor alpha; D007529:Isoflavones; D048789:Phytoestrogens; D010936:Plant Extracts