Cancer-preventive isothiocyanates: dichotomous modulators of oxidative stress

Isothiocyanates (ITCs), a class of phytochemicals with promising cancer-preventive potential, are double-edged swords in the modulation of cellular oxidative stress. While ITCs transcriptionally stimulate many antioxidative enzymes and nonenzyme proteins, leading to enhanced protection against oxidative stressors, they also directly alkylate and deplete cellular thiols, damage mitochondria, and elevate reactive oxygen species, leading to cellular stress. These paradoxical effects appear to occur in tandem: exposure of cells to an ITC rapidly leads to an acute increase in stress, which is followed by a delayed but lasting increase in cellular protection against oxidants and carcinogens. Ironically, although ITC-induced stress may lead to oxidative damage, it has become increasingly clear that much of the chemoprotective activity of ITCs stems from the response of cells to the stress induced by these compounds. (C) 2004 Elsevier Inc. All rights reserved.