Water-soluble organotellurium compounds inhibit thioredoxin reductase and the growth of human cancer cells.

Abstract

The thioredoxin system (NADPH, thioredoxin reductase/ thioredoxin) is important for cancer cell growth and inhibition of apoptosis and presents an attractive target for anticancer drug development. Thioredoxin reductase is a selenocysteine-containing flavoenzyme that catalyzes the reduction of oxidized thioredoxin. This enzyme could therefore be used for regulating the activity of the thioredoxin system. Water-soluble organotellurium compounds of the diaryl telluride, alkyl aryl telluride and dialkyl telluride type, carrying sulfopropyl groups, were found to be the most efficient tellurium-based inhibitors of thioredoxin reductase ever tested. Some of the compounds inhibited the enzyme at submicromolar levels. The compounds also inhibited the growth of MCF-7 and HT-29 human cancer cells in culture at the 5-10 microM level but their hydrophilicity seemed to restrict cellular uptake.