Thioredoxin reductase and cancer cell growth inhibition by organotellurium antioxidants

Anticancer Drugs. 2003 Feb;14(2):153-61. doi: 10.1097/00001813-200302000-00009.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antioxidants / chemical synthesis
  • Antioxidants / pharmacology*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / pathology*
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / pharmacology*
  • Oxidation-Reduction
  • Tellurium / chemistry
  • Tellurium / pharmacology*
  • Thioredoxin-Disulfide Reductase / antagonists & inhibitors*
  • Thioredoxins / pharmacology
  • Tumor Cells, Cultured

Substances

  • Antioxidants
  • Enzyme Inhibitors
  • Organometallic Compounds
  • Thioredoxins
  • Thioredoxin-Disulfide Reductase
  • Tellurium