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 microM), the other TrxR inhibitors were inactive in concentrations below about 10 M.
Engman
Lars
L
Department of Organic Chemistry, Institute of Chemistry, Uppsala University, Uppsala, Sweden. Lars.Engman@kemi.uu.se
Al-Maharik
Nawaf
N
McNaughton
Michael
M
Birmingham
Anne
A
Powis
Garth
G
D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D010084:Oxidation-Reduction; D013691:Tellurium / Q000737:chemistry / Q000494:pharmacology*; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors*; D013879:Thioredoxins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D004791:Enzyme Inhibitors; D009942:Organometallic Compounds; D013879:Thioredoxins; D013880:Thioredoxin-Disulfide Reductase; D013691:Tellurium