Chemopreventive functions of isothiocyanates

Numerous animal and epidemiological studies have demonstrated that consumption of cruciferous vegetables is inversely correlated with the cancer incidence. Strong anticarcinogenic activities of cruciferous vegetables are attributed to the high abundance of glucosinolates. Upon consumption, glucosinolates are hydrolyzed into iso-thiocyanates (ITCs), which in turn are conjugated with intracellular glutathione and excreted via mercapturic acid pathway. On the basis of the principle that ITCs can interact with 1,2-benzenedithiole to produce 1,3-benzodithiole-2-thione, a simple high-pressure liquid chromatography-based assay (namely cyclocondensation assay) has been devised to carry out the accurate measurement of the intracellular ITC accumulation. This assay has been adopted to assess the pharmacokinetic profiles of ITCs in humans, to evaluate the enzymatic efficiency of glucosinolate breakdown by myrosinase and to investigate the intracellular absorption and elimination mechanisms of ITCs. In addition, LC-MS-MS has recently been introduced as an alternative quantitative method for ITCs and proved to be superior to cyclocondensation assay, in terms of sensitivity as well as selectivity. Among several possible cellular mechanisms, both the modulation of nuclear factor kappaB (NF-kappaB) and activator protein-1 (AP-1) and the induction of phase II cellular detoxification and antioxidant enzymes (in brief phase II enzymes) have been proposed as potential molecular mechanisms of chemoprevention by ITCs. In the present review, we describe how ITCs modulate the activity of NF-kappaB and AP-1 and discuss how Nrf2/ARE module was discovered as the central core in the transcriptional regulation of phase II cellular detoxification and antioxidant enzymes.