Thioredoxin reductase and cancer cell growth inhibition by organotellurium antioxidants

Thioredoxin (Trx) expression is increased in several human primary cancers and the Trx/Trx reductase (TrxR) system therefore provides an attractive target for cancer drug development. Novel organotellurium antioxidants, especially a primitive analog of vitamin E (compound 1d) and compounds 7, 9 and 10 - all carrying highly functionalized 4-(dialkylamino)phenyltelluro groups to secure high antioxidative capacity - were found to inhibit TrxR with IC₅₀ values in the low micromolar range. Whereas antioxidant 1d also inhibited the growth of MCF-7 human breast cancer cells in culture at a similar level (IC₅₀ = 1.8 μM), the other TrxR inhibitors were inactive in concentrations below about 10 μM.