Auraptene is an inhibitor of cholesterol esterification and a modulator of estrogen receptors.

Abstract : Auraptene is a prenyloxycoumarin from Citrus spp with chemopreventive properties against colitis-related colon and breast cancers through a yet undefined mechanism. To decipher its mechanism of action, we have used a ligand-structure based approach. We established that auraptene fits with a pharmacophore involved in both the inhibition of Acyl-CoA:Cholesterol Acyl Transferase (ACAT) and the modulation of estrogen receptors (ER). We confirmed experimentally that auraptene inhibits ACAT and binds to ERs in a concentration-dependent manner and that it inhibited ACAT in rat liver microsomes as well as in intact cancer cells of murine and human origins, with an IC(50) in the muM range. Auraptene bound to ERs with affinities of 7.8 muM for ERalpha and 7.9 muM for ERbeta, stabilized ERs and modulated their transcriptional activity via an ER-dependent reporter gene as well as endogenous genes. We further established that these effects correlated well with the control of growth and invasiveness of tumor cells. Our data shed light on the molecular mechanism underlying the anticancer and chemopreventive effects of auraptene.