Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
AAAS Promotion

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 23 April 2004:
Vol. 304. no. 5670, pp. 600 - 602
DOI: 10.1126/science.1093941
Prev | Table of Contents | Next

Reports

Curcumin, a Major Constituent of Turmeric, Corrects Cystic Fibrosis Defects

Marie E. Egan,1,2 Marilyn Pearson,1 Scott A. Weiner,1 Vanathy Rajendran,2 Daniel Rubin,1 Judith Glöckner-Pagel,2 Susan Canny,2 Kai Du,3 Gergely L. Lukacs,3 Michael J. Caplan2*

Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation, {Delta}F508, results in the production of a misfolded CFTR protein that is retained in the endoplasmic reticulum and targeted for degradation. Curcumin is a nontoxic Ca–adenosine triphosphatase pump inhibitor that can be administered to humans safely. Oral administration of curcumin to homozygous {Delta}F508 CFTR mice in doses comparable, on a weight-per-weight basis, to those well tolerated by humans corrected these animals' characteristic nasal potential difference defect. These effects were not observed in mice homozygous for a complete knockout of the CFTR gene. Curcumin also induced the functional appearance of {Delta}F508 CFTR protein in the plasma membranes of transfected baby hamster kidney cells. Thus, curcumin treatment may be able to correct defects associated with the homozygous expression of {Delta}F508 CFTR.

1 Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, Post Office Box 208026, New Haven, CT 06520–8026, USA.
2 Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, Post Office Box 208026, New Haven, CT 06520–8026, USA.
3 Program in Cell and Lung Biology, Hospital for Sick Children, Research Institute, Department of Laboratory Medicine and Pathobiology, University of Toronto, McMaster Building, Room 2032F, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.

* To whom correspondence should be addressed. E-mail: michael.caplan{at}yale.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Role of N-linked oligosaccharides in the biosynthetic processing of the cystic fibrosis membrane conductance regulator.
X.-b. Chang, A. Mengos, Y.-x. Hou, L. Cui, T. J. Jensen, A. Aleksandrov, J. R. Riordan, and M. Gentzsch (2008)
J. Cell Sci. 121, 2814-2823
   Abstract »    Full Text »    PDF »
Complementation of a pathogenic IFNGR2 misfolding mutation with modifiers of N-glycosylation.
G. Vogt, J. Bustamante, A. Chapgier, J. Feinberg, S. Boisson Dupuis, C. Picard, N. Mahlaoui, L. Gineau, A. Alcais, C. Lamaze, et al. (2008)
J. Exp. Med. 205, 1729-1737
   Abstract »    Full Text »    PDF »
Chemical conjugation of {Delta}F508-CFTR corrector deoxyspergualin to transporter human serum albumin enhances its ability to rescue Cl- channel functions.
C. Norez, M. Pasetto, M. C. Dechecchi, E. Barison, C. Anselmi, A. Tamanini, F. Quiri, L. Cattel, P. Rizzotti, F. Dosio, et al. (2008)
Am J Physiol Lung Cell Mol Physiol 295, L336-L347
   Abstract »    Full Text »    PDF »
Parallel Improvement of Sodium and Chloride Transport Defects by Miglustat (n-Butyldeoxynojyrimicin) in Cystic Fibrosis Epithelial Cells.
S. Noel, M. Wilke, A. G. M. Bot, H. R. De Jonge, and F. Becq (2008)
J. Pharmacol. Exp. Ther. 325, 1016-1023
   Abstract »    Full Text »    PDF »
The Mechanism of Cystic Fibrosis Transmembrane Conductance Regulator Transcriptional Repression during the Unfolded Protein Response.
R. Bartoszewski, A. Rab, G. Twitty, L. Stevenson, J. Fortenberry, A. Piotrowski, J. P. Dumanski, and Z. Bebok (2008)
J. Biol. Chem. 283, 12154-12165
   Abstract »    Full Text »    PDF »
Proteasome-Dependent Pharmacological Rescue of Cystic Fibrosis Transmembrane Conductance Regulator Revealed by Mutation of Glycine 622.
C. Norez, F. Bilan, A. Kitzis, Y. Mettey, and F. Becq (2008)
J. Pharmacol. Exp. Ther. 325, 89-99
   Abstract »    Full Text »    PDF »
Structural Analog of Sildenafil Identified as a Novel Corrector of the F508del-CFTR Trafficking Defect.
R. Robert, G. W. Carlile, C. Pavel, N. Liu, S. M. Anjos, J. Liao, Y. Luo, D. Zhang, D. Y. Thomas, and J. W. Hanrahan (2008)
Mol. Pharmacol. 73, 478-489
   Abstract »    Full Text »    PDF »
Curcumin Protects the Rat Liver from CCl4-Caused Injury and Fibrogenesis by Attenuating Oxidative Stress and Suppressing Inflammation.
Y. Fu, S. Zheng, J. Lin, J. Ryerse, and A. Chen (2008)
Mol. Pharmacol. 73, 399-409
   Abstract »    Full Text »    PDF »
A monoclonal antibody prevents aggregation of the NBD1 domain of the cystic fibrosis transmembrane conductance regulator.
V. Lovato, C. Roesli, J. Ahlskog, J. Scheuermann, and D. Neri (2007)
Protein Eng. Des. Sel. 20, 607-614
   Abstract »    Full Text »    PDF »
Modulatory Proteins Can Rescue a Trafficking Defective Epileptogenic Nav1.1 Na+ Channel Mutant.
R. Rusconi, P. Scalmani, R. R. Cassulini, G. Giunti, A. Gambardella, S. Franceschetti, G. Annesi, E. Wanke, and M. Mantegazza (2007)
J. Neurosci. 27, 11037-11046
   Abstract »    Full Text »    PDF »
Chimeric constructs endow the human CFTR Cl channel with the gating behavior of murine CFTR.
T. S. Scott-Ward, Z. Cai, E. S. Dawson, A. Doherty, A. Carina Da Paula, H. Davidson, D. J. Porteous, B. J. Wainwright, M. D. Amaral, D. N. Sheppard, et al. (2007)
PNAS 104, 16365-16370
   Abstract »    Full Text »    PDF »
Processing and function of CFTR-{Delta}F508 are species-dependent.
L. S. Ostedgaard, C. S. Rogers, Q. Dong, C. O. Randak, D. W. Vermeer, T. Rokhlina, P. H. Karp, and M. J. Welsh (2007)
PNAS 104, 15370-15375
   Abstract »    Full Text »    PDF »
Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies.
S. Salvioli, E. Sikora, E. L. Cooper, and C. Franceschi (2007)
Evid. Based Complement. Altern. Med. 4, 181-190
   Abstract »    Full Text »    PDF »
Modulating the Folding of P-Glycoprotein and Cystic Fibrosis Transmembrane Conductance Regulator Truncation Mutants with Pharmacological Chaperones.
Y. Wang, T. W. Loo, M. C. Bartlett, and D. M. Clarke (2007)
Mol. Pharmacol. 71, 751-758
   Abstract »    Full Text »    PDF »
Curcumin Opens Cystic Fibrosis Transmembrane Conductance Regulator Channels by a Novel Mechanism That Requires neither ATP Binding nor Dimerization of the Nucleotide-binding Domains.
W. Wang, K. Bernard, G. Li, and K. L. Kirk (2007)
J. Biol. Chem. 282, 4533-4544
   Abstract »    Full Text »    PDF »
Cystic Fibrosis Mouse Models.
C. Guilbault, Z. Saeed, G. P. Downey, and D. Radzioch (2007)
Am. J. Respir. Cell Mol. Biol. 36, 1-7
   Abstract »    Full Text »    PDF »
An Extract from the Medicinal Plant Phyllanthus acidus and Its Isolated Compounds Induce Airway Chloride Secretion: A Potential Treatment for Cystic Fibrosis.
M. Sousa, J. Ousingsawat, R. Seitz, S. Puntheeranurak, A. Regalado, A. Schmidt, T. Grego, C. Jansakul, M. D. Amaral, R. Schreiber, et al. (2007)
Mol. Pharmacol. 71, 366-376
   Abstract »    Full Text »    PDF »
Rescue of {Delta}F508-CFTR trafficking and gating in human cystic fibrosis airway primary cultures by small molecules.
F. Van Goor, K. S. Straley, D. Cao, J. Gonzalez, S. Hadida, A. Hazlewood, J. Joubran, T. Knapp, L. R. Makings, M. Miller, et al. (2006)
Am J Physiol Lung Cell Mol Physiol 290, L1117-L1130
   Abstract »    Full Text »    PDF »
Rescue of {Delta}F508-CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) by Curcumin: Involvement of the Keratin 18 Network.
J. Lipecka, C. Norez, N. Bensalem, M. Baudouin-Legros, G. Planelles, F. Becq, A. Edelman, and N. Davezac (2006)
J. Pharmacol. Exp. Ther. 317, 500-505
   Abstract »    Full Text »    PDF »
Chemosensitization to cisplatin by inhibitors of the Fanconi anemia/BRCA pathway..
D. Chirnomas, T. Taniguchi, M. de la Vega, A. P. Vaidya, M. Vasserman, A.-R. Hartman, R. Kennedy, R. Foster, J. Mahoney, M. V. Seiden, et al. (2006)
Mol. Cancer Ther. 5, 952-961
   Abstract »    Full Text »    PDF »
Regulatory T Cells, a Potent Immunoregulatory Target for CAM Researchers: The Ultimate Antagonist (I)..
A. Vojdani and J. Erde (2006)
Evid. Based Complement. Altern. Med. 3, 25-30
   Abstract »    Full Text »    PDF »
SERCA Pump Inhibitors Do Not Correct Biosynthetic Arrest of {Delta}F508 CFTR in Cystic Fibrosis.
B. R. Grubb, S. E. Gabriel, A. Mengos, M. Gentzsch, S. H. Randell, A. M. Van Heeckeren, M. R. Knowles, M. L. Drumm, J. R. Riordan, and R. C. Boucher (2006)
Am. J. Respir. Cell Mol. Biol. 34, 355-363
   Abstract »    Full Text »    PDF »
Assessment of cystic fibrosis transmembrane conductance regulator (CFTR) activity in CFTR-null mice after bone marrow transplantation.
E. M. Bruscia, J. E. Price, E.-C. Cheng, S. Weiner, C. Caputo, E. C. Ferreira, M. E. Egan, and D. S. Krause (2006)
PNAS 103, 2965-2970
   Abstract »    Full Text »    PDF »
Most LQT2 Mutations Reduce Kv11.1 (hERG) Current by a Class 2 (Trafficking-Deficient) Mechanism.
C. L. Anderson, B. P. Delisle, B. D. Anson, J. A. Kilby, M. L. Will, D. J. Tester, Q. Gong, Z. Zhou, M. J. Ackerman, and C. T. January (2006)
Circulation 113, 365-373
   Abstract »    Full Text »    PDF »
Curcumin, An Atoxic Antioxidant and Natural NF{kappa}B, Cyclooxygenase-2, Lipooxygenase, and Inducible Nitric Oxide Synthase Inhibitor: A Shield Against Acute and Chronic Diseases.
S. Bengmark (2006)
JPEN J Parenter Enteral Nutr 30, 45-51
   Abstract »    Full Text »    PDF »
Rescue of Vasopressin V2 Receptor Mutants by Chemical Chaperones: Specificity and Mechanism.
J. H. Robben, M. Sze, N.V.A.M. Knoers, and P.M.T. Deen (2006)
Mol. Biol. Cell 17, 379-386
   Abstract »    Full Text »    PDF »
Ubiquitylation of Ion Channels.
H. Abriel and O. Staub (2005)
Physiology 20, 398-407
   Abstract »    Full Text »    PDF »
Curcumin: Getting Back to the Roots.
S. SHISHODIA, G. SETHI, and B. B. AGGARWAL (2005)
Ann. N.Y. Acad. Sci. 1056, 206-217
   Abstract »    Full Text »    PDF »
Assessment of hypoxia in children with cystic fibrosis.
D S Urquhart, H Montgomery, and A Jaffe (2005)
Arch. Dis. Child. 90, 1138-1143
   Abstract »    Full Text »    PDF »
Brugada syndrome and fever: Genetic and molecular characterization of patients carrying SCN5A mutations.
D. I. Keller, J.-S. Rougier, J. P. Kucera, N. Benammar, V. Fressart, P. Guicheney, A. Madle, M. Fromer, J. Schlapfer, and H. Abriel (2005)
Cardiovasc Res 67, 510-519
   Abstract »    Full Text »    PDF »
Hemin induces active chloride secretion in Caco-2 cells.
A. Uc, R. F. Husted, R. L. Giriyappa, B. E. Britigan, and J. B. Stokes (2005)
Am J Physiol Gastrointest Liver Physiol 289, G202-G208
   Abstract »    Full Text »    PDF »
Thioredoxin Reductase Is Irreversibly Modified by Curcumin: A NOVEL MOLECULAR MECHANISM FOR ITS ANTICANCER ACTIVITY.
J. Fang, J. Lu, and A. Holmgren (2005)
J. Biol. Chem. 280, 25284-25290
   Abstract »    Full Text »    PDF »
Activating Cystic Fibrosis Transmembrane Conductance Regulator Channels with Pore Blocker Analogs.
W. Wang, G. Li, J. P. Clancy, and K. L. Kirk (2005)
J. Biol. Chem. 280, 23622-23630
   Abstract »    Full Text »    PDF »
Most F508del-CFTR Is Targeted to Degradation at an Early Folding Checkpoint and Independently of Calnexin.
C. M. Farinha and M. D. Amaral (2005)
Mol. Cell. Biol. 25, 5242-5252
   Abstract »    Full Text »    PDF »
Cystic Fibrosis.
S. M. Rowe, S. Miller, and E. J. Sorscher (2005)
N. Engl. J. Med. 352, 1992-2001
   Full Text »    PDF »
Primum Non Nocere: Does the Current Research Publication System (or the Lay Press) Harm Our Patients?.
J. Davies and A. Bush (2005)
Am. J. Respir. Crit. Care Med. 171, 937-938
   Full Text »    PDF »
Baicalein, a component of Scutellaria radix from Huang-Lian-Jie-Du-Tang (HLJDT), leads to suppression of proliferation and induction of apoptosis in human myeloma cells.
Z. Ma, K.-i. Otsuyama, S. Liu, S. Abroun, H. Ishikawa, N. Tsuyama, M. Obata, F.-J. Li, X. Zheng, Y. Maki, et al. (2005)
Blood 105, 3312-3318
   Abstract »    Full Text »    PDF »
Salivary secretion assay for drug efficacy for cystic fibrosis in mice.
J. A. Best and P. M Quinton (2005)
Exp Physiol 90, 189-193
   Abstract »    Full Text »    PDF »
Curcumin Stimulates Cystic Fibrosis Transmembrane Conductance Regulator Cl- Channel Activity.
A. L. Berger, C. O. Randak, L. S. Ostedgaard, P. H. Karp, D. W. Vermeer, and M. J. Welsh (2005)
J. Biol. Chem. 280, 5221-5226
   Abstract »    Full Text »    PDF »
Varied Mechanisms Underlie the Free Sialic Acid Storage Disorders.
C. C. Wreden, M. Wlizla, and R. J. Reimer (2005)
J. Biol. Chem. 280, 1408-1416
   Abstract »    Full Text »    PDF »
Localization and functional analyses of the MLC1 protein involved in megalencephalic leukoencephalopathy with subcortical cysts.
O. Teijido, A. Martinez, M. Pusch, A. Zorzano, E. Soriano, J. A. del Rio, M. Palacin, and R. Estevez (2004)
Hum. Mol. Genet. 13, 2581-2594
   Abstract »    Full Text »    PDF »
Lung Inflammation as a Therapeutic Target in Cystic Fibrosis.
D. R. Koehler, G. P. Downey, N. B. Sweezey, A. K. Tanswell, and J. Hu (2004)
Am. J. Respir. Cell Mol. Biol. 31, 377-381
   Abstract »    Full Text »    PDF »
Evidence against the Rescue of Defective {Delta}F508-CFTR Cellular Processing by Curcumin in Cell Culture and Mouse Models.
Y. Song, N. D. Sonawane, D. Salinas, L. Qian, N. Pedemonte, L. J. V. Galietta, and A. S. Verkman (2004)
J. Biol. Chem. 279, 40629-40633
   Abstract »    Full Text »    PDF »
Can Curcumin Cure Cystic Fibrosis?.
P. Zeitlin (2004)
N. Engl. J. Med. 351, 606-608
   Full Text »    PDF »
Nontoxic Herbal Extract Protects Mice with Cystic Fibrosis.
(2004)
Journal Watch (General) 2004, 4
   Full Text »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)