ABSTRACT
Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)-butane, SF] is a plantderived aliphatic isothiocyanate (ITC), first isolated as an antimicrobial agent from the leaves of hoary cress and other plants by Procháska and coworkers in the late 1950s [1-4]. However, its cancer chemopreventive activity was not recognized until 1992, when it was found to be the principal ingredient of broccoli extracts exhibiting potent induction of phase 2 detoxification enzymes [5]. In plants, SF and other ITCs are synthesized and stored in cells as a glucosinolate (glucoraphanin in the case of sulforaphane) (Fig. 1), and a large of number of plants are known to contain glucoraphanin [6]. The anionic and nonelectrophilic glucoraphanin is highly water soluble and heat stable. In contrast, SF possesses an isothiocyanate, -N=C=S, group that is highly electrophilic, reacting with sulfur-, nitrogen-and oxygen-based nucleophiles, and heat labile (giving rise primarily to a thiourea derivative, whose biological properties are unknown) [7]. Glucoraphanin is but one of the more than 100 glucosinolates that are synthesized in plants [6, 8]; many are of interest since anticarcinogenic activity has been observed in more than 20 ITCs [9-11]. Although intact glucosinolates are generally assumed to be biologically inert, the anticarcinogenic activity of intact glucoraphanin cannot be completely ruled out [12]. Conversion of glucosinolates to ITCs and other products occurs when plant cells are disrupted, such as by chewing or chopping, and is catalyzed by thioglucoside glucohydrolase (EC 3.2.3.1), commonly known as myrosinase. Myrosinase and the coexisting glucosinolates are physically segregated from one another in normal plant cells, but come into contact when the cells are damaged. In addition to ITCs, hydrolysis of glucosinolates by myrosinase may also give rise to thiocyanates, nitriles, and other products [13], and some (notably indoles) may undergo subsequent chemical reaction. In addition to the formation of SF, enzymatic hydrolysis of glucoraphanin has been shown to yield a nitrile [CH3−(SO)−CH2−CH2−CH2−CH2−CN] as a minor product [14, 15], which seems to lack anticarcinogenic activity [16]. Myrosinase is also present in
enteric microflora, and a significant portion of orally ingested glucoraphanin (10-20%) in humans can be converted to SF in the intestine [17-19].
