Inhibition of estrogen action by 2-phenylchromone as AhR agonist in MCF-7 cells.

Abstract Large amounts of phytoestrogen, a group of estrogen derived from plant sources, are taken from the diet by Asians, but a sign of feminization has not been fully recognized. In this study, we found that some flavonoids inhibited an effect on estrogen action without estrogen receptor (ER) binding. Considering the report that dioxin, an aryl hydrocarbon receptor (AhR) agonist, disrupts the transcriptional activity of ER without binding to the ER, 14 flavonoids were examined for the transcriptional activity of AhR by the yeast reporter assay (AhR). Among them, 2-phenylchromone (flavone, FLA) showed the highest activity. FLA increased the expression of CYP1A1 mRNA, and inhibited the expression of progesterone receptor and pS2 mRNA in MCF-7 cells via non-ER-mediated pathway. Further studies showed that FLA had agonist activity for AhR and enhanced the proteosome-dependent degradation of ERα protein. Thus, FLA inhibited the estrogen action without binding to the ER by acting as a competitive agonist for AhR, which meaning that there can be anti-estrogenic flavonoids such as FLA as well as estrogenic ones such as isoflavones.