title: Curcumin and genistein: the combined effects on disease-associated CFTR mutants and their clinical implications.
abstract: Genistein and curcumin are major components of Asian foods, soybean and curry turmeric respectively. These compounds have been intensively investigated for their chemical and biological features conferring their anti-cancer activity. Genistein and curcumin have also been investigated for their potentiation effects on disease-associated CFTR mutants such as ΔF508 and G551D. Recently, we investigated the combined effect of genistein and curcumin on G551D-CFTR, which exhibits gating defects without abnormalities in protein synthesis or trafficking using the patch-clamp technique. We found that genistein and curcumin showed additive effects on their potentiation of G551D-CFTR in high concentration range and also, more importantly, showed a significant synergistic effect in their minimum concentration ranges. These results are consistent with the idea that multiple mechanisms are involved in the action of these CFTR potentiators. In this review, we revisit the pharmacology of genistein and curcumin on CFTR and also propose new pharmaceutical implications of combined use of these compounds in the development of drugs for CF pharmacotherapy.
authors: Department of Pharmacology, Keio University School of Medicine 35 Shinanomachi, Shinjuku, Tokyo, Japan. yoshiros@sc.itc.keio.ac.jp
authors: Yoshiro
authors: Y
authors: Sohma
authors: Ying-Chun
authors: YC
authors: Yu
authors: Tzyh-Chang
authors: TC
authors: Hwang
mesh_terms: D000818:Animals; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055808:Drug Discovery; D004357:Drug Synergism; D019833:Genistein / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008958:Models, Molecular; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D009154:Mutation; D018408:Patch-Clamp Techniques; D011487:Protein Conformation
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D019833:Genistein; D003474:Curcumin