Curcumin and genistein: The combined effects on disease-associated CFTR mutants and their clinical implications

Current Pharmaceutical Design

Volumn 19, Issue 19, 2013, Pages 3521-3528

  Sohma, Yoshiro ^a,b   Yu, Ying Chun ^a   Hwang, Tzyh Chang ^b,c  

^a KEIO UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^b UNIVERSITY OF MISSOURI   (United States)

^c University of Missouri   (United States)

Author keywords

Additive effect; G551D; Synergistic effect

Indexed keywords

CURCUMIN; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; GENISTEIN; IVACAFTOR; LUMACAFTOR;

CYSTIC FIBROSIS; DRUG EFFECT; DRUG POTENTIATION; GENE MUTATION; HUMAN; PRIORITY JOURNAL; PROTEIN STRUCTURE; REVIEW; ANIMAL; CHANNEL GATING; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DEVELOPMENT; GENETICS; MEMBRANE POTENTIAL; METABOLISM; MOLECULARLY TARGETED THERAPY; MUTATION; PATCH CLAMP; PROTEIN CONFORMATION;

ANIMALS; CURCUMIN; CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; DRUG DISCOVERY; DRUG SYNERGISM; GENISTEIN; HUMANS; ION CHANNEL GATING; MEMBRANE POTENTIALS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; MOLECULAR TARGETED THERAPY; MUTATION; PATCH-CLAMP TECHNIQUES; PROTEIN CONFORMATION;

EID: 84887394805     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/13816128113199990320     Document Type: Review

References (77)

1. Gadsby DC, Vergani P, Csanady L. The ABC protein turned chloride channel whose failure causes cystic fibrosis. Nature 2006; 440: 477-83.
2. Riordan JR, Rommens JM, Kerem B, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 1989; 245: 1066-73.
3. Welsh MJ, Smith AE. Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis. Cell 1993; 73: 1251-4.
4. Gray MA, Greenwell JR, Argent BE. Secretin-regulated chloride channel on the apical plasma membrane of pancreatic duct cells. J Membr Biol 1988; 105: 131-42.
5. Knowles MR, Stutts MJ, Spock A, Fischer N, Gatzy JT, Boucher RC. Abnormal ion permeation through cystic fibrosis respiratory epithelium. Science 1983; 221: 1067-70.
6. Quinton PM. Missing Cl conductance in cystic fibrosis. Am J Physiol 1986; 251: C649-52.
7. Welsh MJ, Liedtke CM. Chloride and potassium channels in cystic fibrosis airway epithelia. Nature 1986; 322: 467-70.
8. Wong PY. CFTR gene and male fertility. Mol Hum Reprod 1998; 4: 107-10.
9. Amaral MD, Kunzelmann K. Molecular targeting of CFTR as a therapeutic approach to cystic fibrosis. Trends Pharmacol Sci 2007; 28: 334-41.
10. Verkman AS, Galietta LJ. Chloride channels as drug targets. Nat Rev Drug Discov 2009; 8: 153-71.
11. Pedemonte N, Zegarra-Moran O, Galietta LJ. High-throughput screening of libraries of compounds to identify CFTR modulators. Methods Mol Biol 2011; 741: 13-21.
12. Van Goor F, Hadida S, Grootenhuis PD, et al. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Natl Acad Sci USA 2009; 106: 18825-30.
13. Van Goor F, Hadida S, Grootenhuis PD, et al. Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc Natl Acad Sci USA 2011; 108: 18843-8.
14. Accurso FJ, Rowe SM, Clancy JP, et al. Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N Engl J Med 2010; 363: 1991-2003.
15. Clancy JP, Rowe SM, Accurso FJ, et al. Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the F508del-CFTR mutation. Thorax 2012; 67: 12-8.
16. Rosenberg MF, O'Ryan LP, Hughes G, et al. The cystic fibrosis transmembrane conductance regulator (CFTR): three-dimensional structure and localization of a channel gate. J Biol Chem 2011; 286: 42647-54.
17. Dawson RJ, Locher KP. Structure of a bacterial multidrug ABC transporter. Nature 2006; 443: 180-5.
18. Aller SG, Yu J, Ward A, et al. Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science 2009; 323: 1718-22.
19. Hwang TC, Sheppard DN. Gating of the CFTR Cl-channel by ATP-driven nucleotide-binding domain dimerisation. J Physiol 2009; 587: 2151-61.
20. Tsai MF, Li M, Hwang TC. Stable ATP binding mediated by a partial NBD dimer of the CFTR chloride channel. J Gen Physiol 2010; 135: 399-414.
21. Tsai MF, Shimizu H, Sohma Y, Li M, Hwang TC. State-dependent modulation of CFTR gating by pyrophosphate. J Gen Physiol 2009; 133: 405-19.
22. Zhou Z, Wang X, Liu HY, Zou X, Li M, Hwang TC. The two ATP binding sites of cystic fibrosis transmembrane conductance regulator (CFTR) play distinct roles in gating kinetics and energetics. J Gen Physiol 2006; 128: 413-22.
23. Shimizu H, Yu YC, Kono K, et al. A stable ATP binding to the nucleotide binding domain is important for reliable gating cycle in an ABC transporter CFTR. J Physiol Sci 2010; 60: 353-62.
24. Cheng SH, Rich DP, Marshall J, Gregory RJ, Welsh MJ, Smith AE. Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel. Cell 1991; 66: 1027-36.
25. Mense M, Vergani P, White DM, Altberg G, Nairn AC, Gadsby DC. In vivo phosphorylation of CFTR promotes formation of a nucleotide-binding domain heterodimer. EMBO J 2006; 25: 4728-39.
26. Baker JM, Hudson RP, Kanelis V, et al. CFTR regulatory region interacts with NBD1 predominantly via multiple transient helices. Nat Struct Mol Biol 2007; 14: 738-45.
27. Wang W, Wu J, Bernard K, et al. ATP-independent CFTR channel gating and allosteric modulation by phosphorylation. Proc Natl Acad Sci USA 2010; 107: 3888-93.
28. Vergani P, Lockless SW, Nairn AC, Gadsby DC. CFTR channel opening by ATP-driven tight dimerization of its nucleotide-binding domains. Nature 2005; 433: 876-80.
29. Jih KY, Sohma Y, Li M, Hwang TC. Identification of a novel posthydrolytic state in CFTR gating. J Gen Physiol 2012; 139: 359-70.
30. Jih KY, Sohma Y, Hwang TC. Nonintegral stoichiometry in CFTR gating revealed by a pore-lining mutation. J Gen Physiol 2012; 140: 347-59.
31. Zielenski J, Tsui LC. Cystic fibrosis: genotypic and phenotypic variations. Annu Rev Genet 1995; 29: 777-807.
32. Chang XB, Tabcharani JA, Hou YX, et al. Protein kinase A (PKA) still activates CFTR chloride channel after mutagenesis of all 10 PKA consensus phosphorylation sites. J Biol Chem 1993; 268: 11304-11.
33. Cutting GR, Kasch LM, Rosenstein BJ, et al. A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein. Nature 1990; 346: 366-9.
34. Li C, Ramjeesingh M, Wang W, et al. ATPase activity of the cystic fibrosis transmembrane conductance regulator. J Biol Chem 1996; 271: 28463-8.
35. Bompadre SG, Sohma Y, Li M, Hwang TC. G551D and G1349D, two CF-associated mutations in the signature sequences of CFTR, exhibit distinct gating defects. J Gen Physiol 2007; 129: 285-98.
36. Cai Z, Taddei A, Sheppard DN. Differential sensitivity of the cystic fibrosis (CF)-associated mutants G551D and G1349D to potentiators of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl-channel. J Biol Chem 2006; 281: 1970-7.
37. Illek B, Fischer H. Flavonoids stimulate Cl conductance of human airway epithelium in vitro and in vivo. Am J Physiol 1998; 275: L902-10.
38. Yu YC, Miki H, Nakamura Y, et al. Curcumin and genistein additively potentiate G551D-CFTR. J Cyst Fibros 2011; 10: 243-52.
39. Ai T, Bompadre SG, Wang X, Hu S, Li M, Hwang TC. Capsaicin potentiates wild-type and mutant cystic fibrosis transmembrane conductance regulator chloride-channel currents. Mol Pharmacol 2004; 65: 1415-26.
40. Pedemonte N, Sonawane ND, Taddei A, et al. Phenylglycine and sulfonamide correctors of defective delta F508 and G551D cystic fibrosis transmembrane conductance regulator chloride-channel gating. Mol Pharmacol 2005; 67: 1797-807.
41. Al-Nakkash L, Springsteel MF, Kurth MJ, Nantz MH. Activation of CFTR by UCCF-029 and genistein. Bioorg Med Chem Lett 2008; 18: 3874-7.
42. Al-Nakkash L, Hu S, Li M, Hwang TC. A common mechanism for cystic fibrosis transmembrane conductance regulator protein activation by genistein and benzimidazolone analogs. J Pharmacol Exp Ther 2001; 296: 464-72.
43. Caci E, Folli C, Zegarra-Moran O, et al. CFTR activation in human bronchial epithelial cells by novel benzoflavone and benzimidazolone compounds. Am J Physiol Lung Cell Mol Physiol 2003; 285: L180-8.
44. Noel S, Faveau C, Norez C, Rogier C, Mettey Y, Becq F. Discovery of pyrrolo[2,3-b]pyrazines derivatives as submicromolar affinity activators of wild type, G551D, and F508del cystic fibrosis transmembrane conductance regulator chloride channels. J Pharmacol Exp Ther 2006; 319: 349-59.
45. Derand R, Bulteau-Pignoux L, Mettey Y, et al. Activation of G551D CFTR channel with MPB-91: regulation by ATPase activity and phosphorylation. Am J Physiol Cell Physiol 2001; 281: C1657-66.
46. Berger AL, Randak CO, Ostedgaard LS, Karp PH, Vermeer DW, Welsh MJ. Curcumin stimulates cystic fibrosis transmembrane conductance regulator Cl-channel activity. J Biol Chem 2005; 280: 5221-6.
47. Bernard K, Wang W, Narlawar R, Schmidt B, Kirk KL. Curcumin cross-links cystic fibrosis transmembrane conductance regulator (CFTR) polypeptides and potentiates CFTR channel activity by distinct mechanisms. J Biol Chem 2009; 284: 30754-65.
48. Dixon RA, Ferreira D. Genistein. Phytochemistry 2002; 60: 205-11.
49. Andersson C, Servetnyk Z, Roomans GM. Activation of CFTR by genistein in human airway epithelial cell lines. Biochem Biophys Res Commun 2003; 308: 518-22.
50. Hwang TC, Wang F, Yang IC, Reenstra WW. Genistein potentiates wild-type and delta F508-CFTR channel activity. Am J Physiol 1997; 273: C988-98.
51. Illek B, Fischer H, Santos GF, Widdicombe JH, Machen TE, Reenstra WW. cAMP-independent activation of CFTR Cl channels by the tyrosine kinase inhibitor genistein. Am J Physiol 1995; 268: C886-93.
52. Illek B, Zhang L, Lewis NC, Moss RB, Dong JY, Fischer H. Defective function of the cystic fibrosis-causing missense mutation G551D is recovered by genistein. Am J Physiol 1999; 277: C833-9.
53. Schmidt A, Hughes LK, Cai Z, et al. Prolonged treatment of cells with genistein modulates the expression and function of the cystic fibrosis transmembrane conductance regulator. Br J Pharmacol 2008; 153: 1311-23.
54. Melin P, Thoreau V, Norez C, Bilan F, Kitzis A, Becq F. The cystic fibrosis mutation G1349D within the signature motif LSHGH of NBD2 abolishes the activation of CFTR chloride channels by genistein. Biochem Pharmacol 2004; 67: 2187-96.
55. Moran O, Galietta LJ, Zegarra-Moran O. Binding site of activators of the cystic fibrosis transmembrane conductance regulator in the nucleotide binding domains. Cell Mol Life Sci 2005; 62: 446-60.
56. Wang F, Zeltwanger S, Yang IC, Nairn AC, Hwang TC. Actions of genistein on cystic fibrosis transmembrane conductance regulator channel gating. Evidence for two binding sites with opposite effects. J Gen Physiol 1998; 111: 477-90.
57. Weinreich F, Wood PG, Riordan JR, Nagel G. Direct action of genistein on CFTR. Pflugers Arch 1997; 434: 484-91.
58. Egan ME, Pearson M, Weiner SA, et al. Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects. Science 2004; 304: 600-2.
59. Lansdell KA, Cai Z, Kidd JF, Sheppard DN. Two mechanisms of genistein inhibition of cystic fibrosis transmembrane conductance regulator Cl-channels expressed in murine cell line. J Physiol 2000; 524 Pt 2: 317-30.
60. Miquel J, Bernd A, Sempere JM, Diaz-Alperi J, Ramirez A. The curcuma antioxidants: pharmacological effects and prospects for future clinical use. A review. Arch Gerontol Geriatr 2002; 34: 37-46.
61. Hwang TC, Koeppe RE, 2nd, Andersen OS. Genistein can modulate channel function by a phosphorylation-independent mechanism: importance of hydrophobic mismatch and bilayer mechanics. Biochemistry 2003; 42: 13646-58.
62. Huang SY, Bolser D, Liu HY, Hwang TC, Zou X. Molecular modeling of the heterodimer of human CFTR's nucleotide-binding domains using a protein-protein docking approach. J Mol Graph Model 2009; 27: 822-8.
63. Derand R, Bulteau-Pignoux L, Becq F. The cystic fibrosis mutation G551D alters the non-Michaelis-Menten behavior of the cystic fibrosis transmembrane conductance regulator (CFTR) channel and abolishes the inhibitory Genistein binding site. J Biol Chem 2002; 277: 35999-6004.
64. Osawa T, Sugiyama Y, Inayoshi M, Kawakishi S. Antioxidative activity of tetrahydrocurcuminoids. Biosci Biotechnol Biochem 1995; 59: 1609-12.
65. Itokawa H, Shi Q, Akiyama T, Morris-Natschke SL, Lee KH. Recent advances in the investigation of curcuminoids. Chin Med 2008; 3: 11.
66. Gopinath D, Ahmed MR, Gomathi K, Chitra K, Sehgal PK, Jayakumar R. Dermal wound healing processes with curcumin incorporated collagen films. Biomaterials 2004; 25: 1911-7.
67. Singh RK, Rai D, Yadav D, Bhargava A, Balzarini J, De Clercq E. Synthesis, antibacterial and antiviral properties of curcumin bioconjugates bearing dipeptide, fatty acids and folic acid. Eur J Med Chem 2010; 45: 1078-86.
68. Ono K, Hasegawa K, Naiki H, Yamada M. Curcumin has potent anti-amyloidogenic effects for Alzheimer's beta-amyloid fibrils in vitro. J Neurosci Res 2004; 75: 742-50.
69. Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 2003; 23: 363-98.
70. Zhou H, Beevers CS, Huang S. The targets of curcumin. Curr Drug Targets 2011; 12: 332-47.
71. Grynkiewicz G, Slifirski P. Curcumin and curcuminoids in quest for medicinal status. Acta Biochim Pol 2012; 59: 201-12.
72. Song Y, Sonawane ND, Salinas D, et al. Evidence against the rescue of defective DeltaF508-CFTR cellular processing by curcumin in cell culture and mouse models. J Biol Chem 2004; 279: 40629-33.
73. Wang W, Bernard K, Li G, Kirk KL. Curcumin opens cystic fibrosis transmembrane conductance regulator channels by a novel mechanism that requires neither ATP binding nor dimerization of the nucleotide-binding domains. J Biol Chem 2007; 282: 4533-44.
74. Mio K, Ogura T, Mio M, et al. Three-dimensional reconstruction of human cystic fibrosis transmembrane conductance regulator chloride channel revealed an ellipsoidal structure with orifices beneath the putative transmembrane domain. J Biol Chem 2008; 283: 30300-10.
75. Zhang L, Aleksandrov LA, Zhao Z, Birtley JR, Riordan JR, Ford RC. Architecture of the cystic fibrosis transmembrane conductance regulator protein and structural changes associated with phosphorylation and nucleotide binding. J Struct Biol 2009; 167: 242-51.
76. Zegarra-Moran O, Romio L, Folli C, et al. Correction of G551DCFTR transport defect in epithelial monolayers by genistein but not by CPX or MPB-07. Br J Pharmacol 2002; 137: 504-12.
77. Hwang TC, Sheppard DN. Molecular pharmacology of the CFTR Cl-channel. Trends Pharmacol Sci 1999; 20: 448-53.