Inhibition of aryl hydrocarbon receptor-dependent transcription by resveratrol or kaempferol is independent of estrogen receptor alpha expression in human breast cancer cells.

摘要

Resveratrol and kaempferol are natural chemopreventative agents that are also aryl hydrocarbon receptor (AHR) antagonists and estrogen receptor (ER) agonists. In this study we evaluated the role of ERalpha in resveratrol- and kaempferol-mediated inhibition of AHR-dependent transcription. Kaempferol or resveratrol inhibited dioxin-induced cytochrome P450 1A1 (CYP1A1) and CYP1B1 expression levels and recruitment of AHR, ERalpha and co-activators to CYP1A1 and CYP1B1. Both phytochemicals induced the expression and recruitment of ERalpha to gene amplified in breast cancer 1 (GREB1). RNAi-mediated knockdown of ERalpha in T-47D cells did not affect the inhibitory action of either phytochemical on AHR activity. Both compounds also inhibited AHR-dependent transcription in ERalpha-negative MDA-MB-231 and BT-549 breast cancer cells. These data show that ERalpha does not contribute to the AHR-inhibitory activities of resveratrol and kaempferol.