Phytochemicals from Cruciferous Plants Protect against Cancer by Modulating Carcinogen Metabolism

Abstract

Several epidemiologic studies suggest that consumption of cruciferous vegetables may be particularly effective (compared with total fruit and vegetable consumption) in reducing cancer risk at several organ sites. Crucifers that are widely consumed are especially rich in glucosinolates, which are converted by plant myrosinase and gastrointestinal microflora to isothiocyanates. A number of isothiocyanates and a limited number of glucosinolates that were examined effectively block chemical carcinogenesis in animal models. Many isothiocyanates are also potent inducers of phase 2 proteins. Substantial evidence supports the view that phase 2 enzyme induction is a highly effective strategy for reducing susceptibility to carcinogens. This conclusion has recently received strong molecular support from experiments on mice in which the specific transcription factor, nrf2, which is essential for induction of phase 2 proteins, was deleted. In these knock-out mice, the basal levels of phase 2 enzymes are very low and not inducible. Accordingly, these mice are much more susceptible than their wild-type counterparts to benzo[a]pyrene forestomach carcinogenesis and are not protected by phase 2 inducers. These experiments provide very strong evidence for a major role of phase 2 enzymes in controlling the risk of exposure to carcinogens. An increasing number of phase 2 proteins that exert a variety of protective mechanisms are being identified. Thus, in addition to detoxifying electrophiles, these proteins exercise versatile, long-lasting and catalytic antioxidant protection.

Season of diagnosis is a prognostic factor in Hodgkin's lymphoma: a possible role of sun-induced vitamin D

“…Owing to vacation, the general health condition may be better at the end of the summer. The intake of vegetables and antioxidants, which is hypothesised to reduce cancer risk (Talalay and Fahey, 2001;Genkinger et al, 2004), may be higher in summer than in winter. However, the data for ovary cancer and bladder cancer (data not shown) argue against these explanations.…”

Glucosinolates inBrassicavegetables: The influence of the food supply chain on intake, bioavailability and human health

“…Glutathione S-transferases (GSTs) are a large multigene family responsible for the elimination of activated carcino- Inverse association for broccoli [283] gens from the body by producing highly polar molecules that are readily excreted [233]. GSTs catalyse this detoxification via the conjugation of carcinogens with GSH.…”

“…Brassica vegetables have been shown to exert protective effects on colon cancer risk in individuals with a specific genotype; however, these effects are dependent on a variety of other variables such as smoking and age [238,239]. The findings of these studies have suggested the positive genotypes are desirable due to an increase in detoxification of carcinogens in these individuals [233], however, in those individuals with the null genotypes, ITCs may act longer due to slower excretion, and exert their effects in a way other than detoxification [188,209,240,241]. In addition to effects on dietary carcinogens, Brassica vegetables have also been demonstrated to alter the metabolism of cigarette smoke carcinogens, such as the nitrosamine (NA), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in humans.…”

The Plastidic Bile Acid Transporter 5 Is Required for the Biosynthesis of Methionine-Derived Glucosinolates inArabidopsis thaliana

“…These compounds and their breakdown products, for example, isothiocyanates, protect plants against herbivores and pathogens (Giamoustaris and Mithen, 1995;Mari et al, 1996;Manici et al, 2000;Reymond et al, 2004;Chung et al, 2005;Mewis et al, 2005;Brader et al, 2006) and are known to serve as human anticancer agents (Talalay and Fahey, 2001;Traw et al, 2003;Hayes et al, 2008). After Met-derived glucosinoates, indolic and benzyl glucosinolates are the most abundant glucosinolates in Arabidopsis.…”