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

Philippe De Medina 1, 2 Salvatore Genovese 3 Michael Paillasse 2 Mahta Mazaheri 4 Stephanie Subra-Caze 4 Kerstin Bystricky 4 Massimo Curini 5 Sandrine Silvente-Poirot 1 Francesco Epifano 3 Marc Poirot 1
1 Departement /u563 : Oncogenèse, Signalisation et Innovation thérapeutique
Centre de Physiopathologie Toulouse Purpan (ex IFR 30 et IFR 150), Institut Claudius Regaud
2 Affichem
3 Dipartimento di Scienze del Farmaco
4 LBME - Laboratoire de biologie moléculaire eucaryote du CNRS
5 Dipartimento di Chimica e Tecnologia del Farmaco
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.
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Article dans une revue
Molecular Pharmacology, American Society for Pharmacology and Experimental Therapeutics, 2010, epub ahead of print. 〈10.1124/mol.110.065250〉
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http://www.hal.inserm.fr/inserm-00519166
Contributeur : Marc Poirot <>
Soumis le : samedi 18 septembre 2010 - 15:43:48
Dernière modification le : mardi 11 septembre 2018 - 16:20:02

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Philippe De Medina, Salvatore Genovese, Michael Paillasse, Mahta Mazaheri, Stephanie Subra-Caze, et al.. Auraptene is an inhibitor of cholesterol esterification and a modulator of estrogen receptors.. Molecular Pharmacology, American Society for Pharmacology and Experimental Therapeutics, 2010, epub ahead of print. 〈10.1124/mol.110.065250〉. 〈inserm-00519166〉

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