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DOI: 10.1055/s-2005-916261
© Georg Thieme Verlag KG Stuttgart · New York
Estrogenic Activity of Isoflavonoids from Onobrychis ebenoides
Publication History
Received: May 18, 2005
Accepted: November 22, 2005
Publication Date:
17 February 2006 (online)
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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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Dr. Michael N. Alexis
Institute of Biological Research and Biotechnology
National Hellenic Research Foundation
11635 Athens
Greece
Phone: +30-210-7273741
Fax: +30-210-7273677
Email: mnalexis@eie.gr
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