Isothiocyanates and Xenobiotic Detoxification

Abstract

The potential of isothiocyanates to antagonize the carcinogenicity of structurally diverse chemicals has been established in animals. A feasible mechanism of action involves protecting DNA by reducing the availability of the genotoxic metabolites of chemical carcinogens by either inhibiting their generation and/or stimulating their detoxification. In vivo as well as in vitro studies conducted in rat/human primary hepatocytes and precision-cut tissue slices have revealed that isothiocyanates can impair cytochrome P450 activity, including the CYP1 family which is the most active in the bioactivation of carcinogens, by virtue of being mechanism-based inactivators. The aromatic phenethyl isothiocyanate is the most effective of those studied, whereas aliphatic isothiocyanates such as sulforaphane and erucin necessitate high doses in order to manifest such effects that may not always be achievable through the diet. In all systems studied, isothiocyanates are strong inducers of detoxification enzyme systems including quinone reductase, glutathione S-transferase, epoxide hydrolase, and UDP-glucuronosyl transferase. Indeed, in smokers phenethyl isothiocyanate intake increases the urinary excretion of inactive mercapturate metabolites of toxic chemicals present in tobacco. Glucosinolates, the precursors of isothiocyanates, have also the potential to upregulate detoxification enzyme systems, but their contribution to the cancer chemoprevention linked to cruciferous vegetable consumption remains to be evaluated.

Sulforaphane Normalizes Intestinal Flora and Enhances Gut Barrier in Mice with BBN‐Induced Bladder Cancer

“…Numerous results from cellular and animal models suggest that SFN possesses potent anticancer activity by directly targeting several molecular mechanisms . The most sensitive target for SFN is the Keap‐1‐ and Nrf‐2‐dependent adaptive stress response system.…”

Induction of Apoptosis and Cytotoxicity by Raphasatin in Human Breast Adenocarcinoma MCF-7 Cells

“…Extensive experimental studies have established that isothiocyanates, both aliphatic and aromatic, such as sulforaphane, erucin, and phenethyl isothiocyanate, owe their potent cancer chemopreventive activity to the fact that they act through a number of mechanisms, modulating favorably the initiation and promotion stages of carcinogenesis [18,22,23,24,25,26,27,28,29,30]. Raphasatin, present in substantial amounts in Daikon (Japanese white radish) as the glucosinolate glucoraphasatin, is consumed extensively in Japan [31].…”

“…Many methods have been developed to evaluate the potential of chemical agents to stimulate apoptosis, including morphological studies, biochemical assays, ELISA, flow cytometry analysis and others, of which morphological studies appear to be the most reliable [17]. As previous studies have demonstrated that isothiocyanates manifest their chemopreventive activity, at least partly, by modulating favorably the processes of apoptosis and cell proliferation [18,19,20,21], the present study was undertaken to establish the potential of GRH and its degradation product raphasatin, to initiate apoptosis and cell cycle arrest in human breast adenocarcinoma (MCF-7) cells.…”

A Review of Dietary (Phyto)Nutrients for Glutathione Support

“…There is a plethora of research to suggest the detoxification and cancer preventative qualities of cruciferous vegetable intake [122,123], especially for cancers related to the gastrointestinal tract [124]. Studies [125,126] have shown that administration of cruciferous-derived compounds, such as sulforaphane, may increase glutathione, glutathione-related enzymes, and even endogenous antioxidant enzymes and inflammatory markers, although results are not always consistent [115]. These compounds may be especially important for individuals with GST polymorphisms.…”