title: Induction of GST and related events by dietary phytochemicals: sources, chemistry, and possible contribution to chemoprevention.
abstract: 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.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Galal
authors.forename: Larry A
authors.initials: LA
authors.lastname: Walker
authors.affiliation: National Center for Natural Products Research and Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University, MS 58677, USA. ikhan@olemiss.edu.
authors.forename: Ikhlas A
authors.initials: IA
authors.lastname: Khan
mesh_terms: D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry; D002453:Cell Cycle / Q000187:drug effects; D002986:Clinical Trials as Topic; D020536:Enzyme Activators / Q000008:administration & dosage / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D050217:Metabolic Detoxication, Phase II / Q000235:genetics; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D064209:Phytochemicals / Q000008:administration & dosage / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D001688:Biological Products; D020536:Enzyme Activators; D064209:Phytochemicals; D017382:Reactive Oxygen Species; D015262:Xenobiotics; D005982:Glutathione Transferase