Thioredoxin reductase and cancer cell growth inhibition by organotellurium antioxidants.

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.

• Authors: Lars Engman, Nawaf Al-Maharik, Michael McNaughton, Anne Birmingham, Garth Powis
• Journal: Anti-cancer drugs (Anticancer Drugs) Vol. 14 Issue 2 Pg. 153-61 (Feb 2003) ISSN: 0959-4973 [Print] England
• PMID: 12569302 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2003 Lippincott Williams & Wilkins

Chemical References

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

Topics

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