Increased functional cell surface expression of CFTR and Delta F508-CFTR by the anthracycline doxorubicin

Abstract

Cystic fibrosis (CF) is a disease that is caused by mutations within the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The most common mutation, Delta F508, accounts for 70% of all CF alleles and results in a protein that is defective in folding and trafficking to the cell surface. However, Delta F508-CFTR is functional when properly localized. We report that a single, noncytotoxic dose of the anthracycline doxorubicin (Dox, 0.25 muM) significantly increased total cellular CFTR protein expression, cell surface CFTR protein expression, and CFTR-associated chloride secretion in cultured T84 epithelial cells. Dox treatment also increased Delta F508-CFTR cell surface expression and Delta F508-CFTR-associated chloride secretion in stably transfected Madin-Darby canine kidney cells. These results suggest that anthracycline analogs may be useful for the clinical treatment of CF.