title: Curcumin and genistein additively potentiate G551D-CFTR.
abstract: BACKGROUND
  The G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) is a common cause of cystic fibrosis (CF). G551D-CFTR is characterized by an extremely low open probability despite its normal trafficking to the plasma membrane. Numerous small molecules have been shown to increase the activity of G551D-CFTR presumably by binding to the CFTR protein.
  
  
  METHODS
  We investigated the effect of curcumin, genistein and their combined application on G551D-CFTR activity using the patch clamp technique.
  
  
  RESULTS
  Curcumin increased G551D-CFTR whole-cell and single-channel currents less than genistein did at their maximally effective concentrations. However, curcumin further increased the channel activity of G551D-CFTR that had been already maximally potentiated by genistein, up to ~50% of the WT-CFTR level. In addition, the combined application of genistein and curcumin over a lower concentration range synergistically rescued the gating defect of G551D-CFTR.
  
  
  CONCLUSIONS
  The additive effects between curcumin and genistein not only support the hypothesis that multiple mechanisms are involved in the action of CFTR potentiators, but also pose pharmaceutical implications in the development of drugs for CF pharmacotherapy.
authors: Department of Pharmacology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan.
authors: Ying-Chun
authors: YC
authors: Yu
authors: Haruna
authors: H
authors: Miki
authors: Yumi
authors: Y
authors: Nakamura
authors: Akiko
authors: A
authors: Hanyuda
authors: Yohei
authors: Y
authors: Matsuzaki
authors: Yoichiro
authors: Y
authors: Abe
authors: Masato
authors: M
authors: Yasui
authors: Kazuhiko
authors: K
authors: Tanaka
authors: Tzyh-Chang
authors: TC
authors: Hwang
authors: Silvia G
authors: SG
authors: Bompadre
authors: Yoshiro
authors: Y
authors: Sohma
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003474:Curcumin / Q000494:pharmacology*; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000502:physiology*; D004357:Drug Synergism; D019833:Genistein / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects*; D020125:Mutation, Missense; D018408:Patch-Clamp Techniques; D048789:Phytoestrogens / Q000494:pharmacology; D014162:Transfection
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C505032:CFTR protein, human; D048789:Phytoestrogens; C485184:enhanced green fluorescent protein; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D049452:Green Fluorescent Proteins; D019833:Genistein; D003474:Curcumin