Water-soluble organotellurium compounds inhibit thioredoxin reductase and the growth of human cancer cells.
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.
Engman
L
L
Uppsala University, Department of Organic Chemistry, Institute of Chemistry, Sweden. lars.engman@kemi.uu.se
Kandra
T
T
Gallegos
A
A
Williams
R
R
Powis
G
G
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D012995:Solubility; D013691:Tellurium / Q000737:chemistry*; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009942:Organometallic Compounds; D013880:Thioredoxin-Disulfide Reductase; D013691:Tellurium