INHIBITION OF CARCINOGENESIS BY ISOTHIOCYANATES*

Abstract

Isothiocyanates occur as conjugates in a wide variety of cruciferous vegetables. Consumption of normal amounts of these vegetables results in the uptake of substantial quantities of isothiocyanates. These naturally occurring isothiocyanates as well as many synthetic analogs can be powerful inhibitors of carcinogenesis in laboratory animals. Particularly impressive results have been obtained in animal models of lung and esophageal cancer. This review summarizes available data on inhibition of carcinogenesis by isothiocyanates. The major mechanism of inhibition appears to be selective inhibition of cytochrome P450 enzymes involved in carcinogen metabolic activation. Evidence for this is reviewed. Isothiocyanates also induce Phase II enzymes and enhance apoptosis. These properties may also be involved in their chemopreventive activity. Phenethyl isothiocyanate is a particularly effective inhibitor of lung tumor induction by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and, therefore, is currently being developed as a chemopreventive agent against lung cancer.