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 α (ERα) were nearly comparable and matched those of 1 - 3 for ERβ, 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 ≥ 2 ≥ 1) matched better that of affinities for ERβ (4 > 3 ≥ 2 ≥ 1) rather than ERα (4 ≥ 3 ≥ 2 ≥ 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 μM. 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.

Abbreviations

AlkP:Alkaline Phosphatase

DCC-FBS:Dextran Coated Charcoal-treated Fetal Bovine Serum

EGF:Epidermal Growth Factor

ER:Estrogen Receptor

ERE:Estrogen Responsive Element

HRT:Hormone Replacement Therapy

RBA:Relative Binding Affinity

Key words

Onobrychis ebenoides - Leguminosae - isoflavones - estrogenic activity

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