Mechanisms of action of isothiocyanates in cancer chemoprevention: an update

Abstract

Isothiocyanates (ITC), derived from glucosinolates, are thought to be responsible for the chemoprotective actions conferred by higher cruciferous vegetable intake. Evidence suggests that isothiocyanates exert their effects through a variety of distinct but interconnected signaling pathways important for inhibiting carcinogenesis, including those involved in detoxification, inflammation, apoptosis, and cell cycle and epigenetic regulation, among others. This article provides an update on the latest research on isothiocyanates and these mechanisms, and points out remaining gaps in our understanding of these events. Given the variety of ITC produced from glucosinolates, and the diverse pathways on which these compounds act, a systems biology approach, in vivo, may help to better characterize their integrated role in cancer prevention. In addition, the effects of dose, duration of exposure, and specificity of different ITC should be considered.

Figure 1

Glucosinolates in cruciferous vegetables can be divided into several sub-groups based on the chemical structure of the side chains.

Figure 2

Conversion of select glucosinolates to their corresponding isothiocyanates.

Figure 3

Mechanisms of action of isothiocyanates in the modulation of signaling pathways involved in cancer chemoprevention. (CYP=cytochrome P450; GST=glutathione S-transferase; UGT=UDP-glucuronosyl transferase; NF-κB=nuclear factor kappa B; HDAC=histone deacetylase; miRNA=micro RNA)