PT - JOURNAL ARTICLE AU - Philippe de Medina AU - Salvatore Genovese AU - Michael R. Paillasse AU - Mahta Mazaheri AU - Stephanie Caze-Subra AU - Kerstin Bystricky AU - Massimo Curini AU - Sandrine Silvente-Poirot AU - Francesco Epifano AU - Marc Poirot TI - Auraptene Is an Inhibitor of Cholesterol Esterification and a Modulator of Estrogen Receptors AID - 10.1124/mol.110.065250 DP - 2010 Nov 01 TA - Molecular Pharmacology PG - 827--836 VI - 78 IP - 5 4099 - http://molpharm.aspetjournals.org/content/78/5/827.short 4100 - http://molpharm.aspetjournals.org/content/78/5/827.full SO - Mol Pharmacol2010 Nov 01; 78 AB - Auraptene is a prenyloxycoumarin from Citrus species with chemopreventive properties against colitis-related colon and breast cancers through a yet-undefined mechanism. To decipher its mechanism of action, we 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 (ERs). 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 and in intact cancer cells of murine and human origins, with an IC50 value in the micromolar range. Auraptene bound to ERs with affinities of 7.8 μM for ERα and 7.9 μM for ERβ, stabilized ERs, and modulated their transcriptional activity via an ER-dependent reporter gene and 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.