Proliferation-stimulating effects of icaritin and desmethylicaritin in MCF-7 cells

Icariin, icaritin and desmethylicaritin are constituents of Epimedium with a similar structure to genistein and daidzein. Using the modified MCF-7 cell proliferation assay (E-SCREEN assessment system), these compounds were tested for their estrogen-like activities. Icaritin and desmethylicaritin, but not icariin, strongly stimulated the proliferation of MCF-7/BUS cells. Cell cycle analysis revealed that the proliferation stimulatory effect was associated with a marked increase in the number of MCF-7/BUS cells in S phase and a significant increase in the G2/M population, with effects similar to those of estradiol. These actions were dose dependent (range from 1 nM to 10 microM) and could be significantly inhibited by the specific estrogen receptor antagonist ICI 182,780 [7 alpha-[9(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl)-estra-1,3,5(10)-triene-3,17beta-diol)]. The estrogen receptor-regulated progesterone receptor and PS2 mRNA levels were increased by treatment with icaritin or desmethylicaritin within 24 h and the effects were also reversed by ICI 182,780. It was concluded that icaritin and desmethylicaritin are novel phytoestrogens and that the estrogenic effects of icaritin and desmethylicaritin are mediated by the estrogen receptor.