Dithiolethiones for Cancer Chemoprevention: Where Do We Stand?

摘要

Dithiolethiones are a well-known class of cancer chemopreventive agents, whose key mechanism of action involves activation of Nrf2 signaling and induction of Phase 2 enzymes. In the past, attention has been focused mainly on 4-methyl-5-pyrazinyl-3H-1,2-dithiole-3-thione (oltipraz), which showed ability as a wide-spectrum inhibitor of chemical carcinogenesis in preclinical models. However, clinical trials of oltipraz have shown questionable efficacy and, at the high doses employed in such studies, significant side effects were observed. Dithiolethiones that are markedly more effective and potent than oltipraz in both induction of Phase 2 enzymes and inhibition of chemical carcinogenesis in preclinical studies have been identified, and these compounds have shown pronounced organ specificity in vivo. Further investigation of these compounds may lead to development of effective and safe agents for cancer prevention in humans.