Licorice root extract and its major isoflavan, glabridin, exhibited varying
degrees of estrogen receptor (ER) agonism in different tissues in vitro an
d in vivo. Animals fed with licorice extract, compared with estradiol and g
labridin, showed an increase in creatine kinase (CK) activity, a known mark
er for estrogen responsive genes, which was higher than expected from the l
evels of glabridin in the extract. This led us to test for other components
that may contribute to this strong estrogen agonist activity. Results indi
cated that glabrene and isoliquiritigenin, (2 ' ,4 ' ,4-three hydroxy chalc
one) (ILC) in the licorice extract can bind to the human ER with higher aff
inity (IC50, 1 and 0.5 muM) than glabridin (IC50, 5 muM). The stimulatory e
ffects of glabrene in vivo were tissue specific and similar to those of est
radiol, The effect of increasing concentrations of glabrene and ILC on the
growth of breast tumor cell were biphasic. Both showed an ER-dependent grow
th-promoting effect at low concentrations (10 nM-10 muM), and ER-independen
t antiproliferative activity at concentrations > 15 muM. This is the first
study to indicate that glabrene, an isoflavene exerted varying degrees of E
R agonism in different tissues. (C) 2001 Elsevier Science Ltd. All rights r
eserved.