Allyl isothiocyanate (AITC), also known as mustard oil, is one of the most common naturally occurring isothiocyanates (ITCs) [1
]. ITCs occur primarily in cruciferous vegetables, many of which show significant cancer chemopreventive activities, and therefore are widely suspected to account in part for the cancer preventive activities of these vegetables in humans [3
]. Sulforaphane is perhaps the most widely known crucifer-derived cancer chemopreventive ITC [4
]. ITCs are synthesized and stored in cruciferous vegetables as glucosinolates (β
-hydroxysulfate), which are believed to be chemically and biologically inert, and formed from the latter when plant tissues are damaged. The conversion is catalyzed by myrosinase (a thioglucoside glucohydrolase), first forming thiohydroximate-O-sulfonates, which rapidly and spontaneously rearrange to give rise to ITCs. Myrosinase coexists with but is physically separated from glucosinolates under normal conditions. Conversion (up to 40%) to ITCs of ingested glucosinolates that escape plant myrosinase may take place in vivo, as the intestinal microflora of both humans and animals also possess myrosinase activity [5
AITC is derived from sinigrin, as shown in , which is the predominant glucosinolate in many commonly consumed cruciferous vegetables, such as Brussels sprouts, cabbage, cauliflower and kale [1
], and are particularly abundant in mustard, horseradish and wasabi [9
]. For example, each gram of fresh wasabi yields as much as 34 μmol sinigrin/AITC [10
]. Conversion of sinigrin to AITC by human microflora myrosinase has been well documented [11
]. However, the yield of AITC in certain vegetables such as cabbage may vary significantly, due to the presence of an epithiospecifier protein, which promotes formation of 1-cyano-2,3-epithiopropane, at the cost of AITC [8
]. Interestingly, a recent study has found that 1-cyano-2,3-epithiopropane induces Phase 2 genes and affords cytoprotection [13
]. AITC is a liquid at ambient temperature (melting point of -80°C) and has a very pungent taste, apparently due to its activation of the transient receptor potential A1 channel (TRPA1) in sensory neurons [14
]. Indeed, AITC is responsible for the pungent taste of the above-mentioned vegetables, and synthetic AITC is sometimes deliberately added to some vegetable products such as a prepared horseradish meal to enhance the flavor. AITC appears to serve the plant as a defense against herbivores, as chewing the plant by the herbivores generates AITC that presumably repels them.
Myrosinase-catalyzed conversion from sinigrin to AITC
Human exposure to AITC is undoubtedly widespread and frequent, as many common cruciferous vegetables are a rich source of AITC, but the exposure levels have not been well documented. A large number of studies on the biological response to AITC have been published, many of which suggest that AITC is a highly attractive cancer chemopreventive agent. But a few other studies also raised the concern of potential toxicity. In this review, the evidence that argues for and against AITC as a cancer chemopreventive agent is presented and discussed: it is divided into five sections, including bioavailability and metabolic disposition of AITC, cellular uptake and tissue distribution of AITC, antimicrobial activity of AITC, anticancer activity of AITC, and dichotomy of cytoprotective activity and toxicity of AITC. To the best of my knowledge, a similar review on AITC has not been published. Hence, this article may be a useful reference on the biological response to AITC, as most if not all of the relevant data are cited and discussed herein.