Natural Compound Curcumin-a Channel Potentiator Rather Than a Corrector of the Defective Intracellular Processing of ΔF508 Mutant Cystic Fibrosis Transmembrane Conductance Regulator

Cystic fibrosis(CF) is a severe genetic disease caused by the gene mutation of the cystic fibrosis transmembrane conductance regulator(CFTR) chloride channel. The most common point mutation ΔF508, which leads to impaired intracellular processing and channel gating of CFTR, appears in about 90% CF patients. The natural compound curcumin was reported to correct the processing defect of ΔF508-CFTR and proposed as a potential therapeutic drug to cure CF. In the present study, we analyzed the effect of curcumin on ΔF508-CFTR and demonstrated that curcumin can restore the impaired chloride conductance of ΔF508 mutant CFTR. The activity is rapid, reversible and cAMP-dependent. However, we couldn't reproduce the previously reported correction of the defective membrane trafficking of ΔF508-CFTR by curcumin. Therefore, curcumin may not be a superior lead compound for developing anti-CF drugs.