Estrogenic and antiproliferative properties of glabridin from licorice in human breast cancer cells

There is an increasing demand for natural compounds that improve women's he alth by mimicking the critical benefits of estrogen to the bones and the ca rdiovascular system but avoiding its deleterious effects on the breast and uterus, The estrogenic properties of glabridin, the major isoflavan in lico rice root, were tested in view of the resemblance of its structure and lipo philicity to those of estradiol, The results indicate that glabridin is a p hytoestrogen, binding to the human estrogen receptor and stimulating creati ne kinase activity in rat uterus, epiphyseal cartilage, diaphyseal bone, ao rta, and left ventricle of the heart. The stimulatory effects of 2.5-25 mug /animal glabridin were similar to those of 5 mug/animal estradiol, Chemical modification of glabridin showed that the position of the hydroxyl groups has a significant role in binding to the human estrogen receptor and in pro liferation-inducing activity, Glabridin was found to be three to four times more active than 2'-O-methylglabridin and 4'-O-methylglabridin, and both d erivatives were more active than 2',4'-O-methylglabridin. The effect of inc reasing concentrations of glabridin on the growth of breast tumor cells was biphasic. Glabridin showed an estrogen receptor-dependent, growth-promotin g effect at low concentrations (10 nM-10 muM) and estrogen receptor-indepen dent antiproliferative activity at concentrations of > 15 muM. This Is the first study to indicate that isoflavans have estrogen-like activities. Glab ridin and its derivatives exhibited varying degrees of estrogen receptor ag onism in different tests and demonstrated growth-inhibitory actions on brea st cancer cells.