title: Tetrahydro-iso-alpha Acids Antagonize Estrogen Receptor Alpha Activity in MCF-7 Breast Cancer Cells.
abstract: Tetrahydro-iso-alpha acids commonly called THIAA or Tetra are modified hop acids extracted from hop (Humulus lupulus L.) which are frequently used in brewing industry mainly in order to provide beer bitterness and foam stability. Interestingly, molecular structure of tetrahydro-iso-alpha acids is close to a new type of estrogen receptor alpha (ERα) antagonists aimed at disrupting the binding of coactivators containing an LxxLL motif (NR-box). In this work we show that THIAA decreases estradiol-stimulated proliferation of MCF-7 (ERα-positive breast cancer cells). Besides, we show that it inhibits ERα transcriptional activity. Interestingly, this extract fails to compete with estradiol for ERα binding and does not significantly impact the receptor turnover rate in MCF-7 cells, suggesting that it does not act like classical antiestrogens. Hence, we demonstrate that THIAA is able to antagonize ERα estradiol-induced recruitment of the LxxLL binding motif.
authors.affiliation: Institut Meurice, 1 avenue Emile Gryzon, 1070 Brussels, Belgium.
authors.forename: Maëlle
authors.initials: M
authors.lastname: Lempereur
authors.affiliation: Institut Meurice, 1 avenue Emile Gryzon, 1070 Brussels, Belgium.
authors.forename: Claire
authors.initials: C
authors.lastname: Majewska
authors.affiliation: Institut Meurice, 1 avenue Emile Gryzon, 1070 Brussels, Belgium.
authors.forename: Amandine
authors.initials: A
authors.lastname: Brunquers
authors.affiliation: Institut Meurice, 1 avenue Emile Gryzon, 1070 Brussels, Belgium.
authors.forename: Sumalee
authors.initials: S
authors.lastname: Wongpramud
authors.affiliation: Institut Meurice, 1 avenue Emile Gryzon, 1070 Brussels, Belgium.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Valet
authors.affiliation: Yakima Chief-Hopunion LLC, 10 avenue A. Fleming, 1348 Louvain-La-Neuve, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Janssens
authors.affiliation: Institut Meurice, 1 avenue Emile Gryzon, 1070 Brussels, Belgium; Commission Communautaire Française (Cocof), Service des Industries Biochimiques, Belgium.
authors.forename: Monique
authors.initials: M
authors.lastname: Dillemans
authors.affiliation: Institut Meurice, 1 avenue Emile Gryzon, 1070 Brussels, Belgium; Commission Communautaire Française (Cocof), Service des Industries Biochimiques, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Van Nedervelde
authors.affiliation: Institut Meurice, 1 avenue Emile Gryzon, 1070 Brussels, Belgium; Commission Communautaire Française (Cocof), Département des Substances Naturelles et de Biochimie, Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: Gallo