Planta Med 2006; 72(6): 488-493
DOI: 10.1055/s-2005-916261
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Estrogenic Activity of Isoflavonoids from Onobrychis ebenoides

Maria Halabalaki1 , Xanthippi Alexi2 , 3 , Nektarios Aligiannis1 , George Lambrinidis4 , Harris Pratsinis5 , Ida Florentin2 , Sofia Mitakou1 , Emmanuel Mikros4 , Alexios-Leandros Skaltsounis1 , Michael N. Alexis2
  • 1Division of Pharmacognosy and Natural Products Chemistry, School of Pharmacy, University of Athens, Athens, Greece
  • 2Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece
  • 3Present address: Cancer Research UK Institute for Cancer Studies, The University of Birmingham, Birmingham, UK
  • 4Division of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Athens, Greece
  • 5Institute of Biology, NCSR ”Demokritos”, Athens, Greece
Further Information

Publication History

Received: May 18, 2005

Accepted: November 22, 2005

Publication Date:
17 February 2006 (online)

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 > 321) matched better that of affinities for ERβ (4 > 321) rather than ERα (4321). 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

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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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