Article,
On the potential of thioredoxin reductase inhibitors for cancer therapy
SEMINARS IN CANCER BIOLOGY, 16 (6): 452-465 (2006)
Abstract
Thioredoxin reductase (TrxR)-as part of a major thiol regulating
system-allows redox metabolism to adjust to cellular requirements.
Therefore, changes at the redox level reflect as a pars pro toto
changes concerning the entire cell. Three different TrxR isoenzymes,
TrxR1 as cytosolic, TrxR2 as mitochondrial, and TrxR3 as
testis-specific thiol regulator are known. All three enzymes contain a
reactive and solvent accessible selenocysteine residue which is located
on a flexible C-terminal arm of the protein. This selenocysteine is
essentially involved in the catalytic cycle of TrxR and thus represents
an attractive binding site for inhibitors. Many tumor cells have
elevated TrxR levels and TrxR has been shown to play a major role in
drug resistance. Inhibition of TrxR and its related redox reactions may
thus contribute to a successful single, combinatory or adjuvant cancer
therapy. A great number of effective natural and synthetic TrxR
inhibitors are now available possessing antitumor pot
