Inhibitory effects of anticancer drugs on cytosolic carbonic anhydrase isozymes

Abstract

Anticancer drugs are widely used cancer treatment. Human carbonic anhydrase I and II were shown widely distribution with erythrocytes so it is important to understand how effect is anticancer drugs these isozymes. In this aim, paclitaxel, irinotecan, oxaliplatin, docetaxel and epirubicin studied in vitro effect on human carbonic anhydrases I and II obtained from human erythrocytes. Carbonic anhydrase isozymes were purified with affinity chromatography by Sepharose 4B-ethylene diamine-4-thioureido benzenesulfanamide gel and the purity of the isozymes has been checked a single band by sodium dodecyl sulphate polyacrylamide gel electrophoresis. IC50 values, inhibition constants (Ki) and inhibition types were determined with anticancer drugs on human carbonic anhydrase I and II. Competitive type inhibition was obtained with irinotecan on human carbonic anhydrase I but uncompetitive inhibition was seen on human carbonic anhydrase II using p-nitrophenyl acetate as a substrate. Non-competitive inhibition type was determined with docataxel, paclitaxel and oxaliplatin on human carbonic anhydrase I and II. Epirubicin was shown uncompetitive inhibition type on studied isozymes. Docataxel showed the greatest inhibition with the IC50 value 8.59 mu mol/L on human carbonic anhydrase I. But there is less inhibition was seen with docataxel for human carbonic anhydrase II. The results of study show that anticancer drugs also have an important role in inhibiting human carbonic anhydrases I and II.