Glyceollins and dehydroglyceollins isolated from soybean act as SERMs and ER subtype-selective phytoestrogens

Seven prenylated 6a-hydroxy-pterocapans and five prenylated 6a,11a-pterocarpenes with different kinds of prenylation were purified from an ethanolic extract of fungus-treated soybean sprouts. The activity of these compounds toward both human estrogen receptors (hER alpha and hER beta) was determined in a yeast bioassay and the activity toward hERa was additionally tested in an U2-OS based hERa CALUX bioassay. In the yeast bioassay, compounds with chain prenylation showed in general an agonistic mode of action toward hERa, whereas furan and pyran prenylation led to an antagonistic mode of action. Five of these antagonistic compounds had an agonistic mode of action in the U2-OS based hER alpha CALUX bioassay, implying that these compounds can act as SERMs. The yeast bioassay also identified 8 ER subtype selective compounds, with either an antagonistic mode of action or no response toward hERa and an agonistic mode of action toward hER beta. The ER subtype-selective compounds were characterized by 6a-hydroxy-pterocarpan or 6a,11a-pterocarpene backbone structure. It is suggested that either the extra D-ring or the increase in length to 12-13.5 angstrom of these compounds is responsible for an agonistic mode of action toward hERS and, thereby, inducing ER subtype-selective behavior. (C) 2015 Elsevier Ltd. All rights reserved.