Induction of GST and Related Events by Dietary Phytochemicals: Sources, Chemistry, and Possible Contribution to Chemoprevention

This review provides an overview of the chemical constituents of regularly consumed plants that increase the activity or induce expression of glutathione S-transferases (GSTs), a major family of detoxification/cytoprotective enzymes of ubiquitous occurrence in the body. Since induction of phase II (cytoprotective) enzymes, essentially GSTs, is a principal strategy in deactivation of potential carcinogens, it is reasonable to conclude that phytochemicals that enhance the activity/expression of GST isoforms/isoenzymes may play a role in cancer prevention. In this respect, classes of natural products that exhibit this ability are presented. In addition, their possible contribution to chemoprevention is discussed. GSTs constitute a large family of detoxification enzymes in nature. GSTs has been long known to deactivate electrophilic xenobiotics or metabolites, reactive oxygen species as well as certain endogenous substrates. However, there is a growing appreciation that GSTs may have an even wider relevance to cancer, in that they can directly modulate the activity of a number of protein targets, including other enzymes in redox pathways and in signaling networks of cell division and cell cycle control. The following aspects will be treated herein: botanical sources, phytochemical classes, chemical structures of these natural products, bioactivity relevant to chemoprevention, and their influence on induction of GST in vitro and in animal models. A hint on the SAR of organosulfur compounds, isothiocyanates, and limonoids as GST inducers, is added. The few clinical and/or epidemiological studies that associate GST induction with prevention of carcinogenesis are also reviewed.