Metabolism of isothiocyanates in individuals with positive and null GSTT1 and M1 genotypes after drinking watercress juice

Abstract

Background & Aims-Isothiocyanates (ITCs) derived from cruciferous vegetables have been shown to be promising agents against cancer in human cell culture, animal models, and in epidemiological studies. Several epidemiological studies have demonstrated an inverse relationship between intake of dietary isothiocyanates and the risk of cancers, particularly lung, colon, and breast. More importantly, the protective effects of dietary ITCs appear to be influenced by glutathione S-transferase (GST) genotype; specifically, individuals with glutathione Stransferase theta 1 (GSTT1) and glutathione S-transferase Mu 1 (GSTM1) null are better protected than those with GSTT1 and M1 positive. Although majority of studies, especially those conducted in populations exposed to ITCs rich diet, demonstrated such effects there are a few studies showed opposite or no association. While evidence for the interactions of dietary ITCs with GST genes is relatively strong, the reasons for the differential effects remain unclear. In this study, we examined one possible mechanism whether subjects with the null genotypes excrete ITCs at a slower rate than those with the positive genotypes after drinking watercress juice, a rich source of ITCs.

2-Phenethyl Isothiocyanate, Glutathione S-transferase M1 and T1 Polymorphisms, and Detoxification of Volatile Organic Carcinogens and Toxicants in Tobacco Smoke

“…Our hypothesis was supported by observational studies reporting that among subjects who consumed similar amounts of cruciferous vegetables, urinary levels of total isothiocyanates were higher in those possessing the GSTM1 and/or GSTT1 gene compared to those who carried neither of these genes (48, 49). This was not confirmed by previous feeding studies (50, 51) or the present study, in which we found little effect of GSTT1 or GSTM1 status on the urinary levels of PEITC-NAC in the individuals treated with PEITC (Supplemental Table S2). Therefore, GSTM1 and GSTT1 status may have little or no effect on circulating levels of PEITC; the level of which in double null individuals are likely from both the non-enzymatic reaction of PEITC with glutathione as well as catalysis of this reaction by GSTP1, which has similar catalytic efficiency to GSTM1 (52).…”

The Anti-Cancer Effect of Watercress (Rorripa Nasturtium Aquaticum) Extract on Breast Cancer Cells

“…Watercress has been eaten for several thousand years and multiple remedial applications are assigned to it during centuries. It has been suggested as an anti-baldness measure by Romans and Anglo-Saxons, as a pure food for ascetic hermits in Ireland, and as a mental stimulant helping decision making in ancient Iran and the Persian king Xerxes made his troops eat it [8,9]. Figure 1 represents the watercress plant.…”

Clinical Trial of 2-Phenethyl Isothiocyanate as an Inhibitor of Metabolic Activation of a Tobacco-Specific Lung Carcinogen in Cigarette Smokers

“…A review of this literature suggests that cruciferous vegetable intake may be weakly and inversely associated with lung cancer risk with the strongest protective association among those with homozygous deletion for both GSTM1 and GSTT1 , based on the hypothesis that these individuals would have more free isothiocyanate available (37). However, Dyba et al did not find any effect of GSTM1 and GSTT1 genotype on excretion of isothiocyanates after consumption of watercress juice, a rich source of PEITC (39). We also did not observe the predicted effect of glutathione S -transferase polymorphisms on PEITC metabolism.…”

“…It has been hypothesized based on epidemiologic studies that individuals with GSTM1 or GSTT1 null-null genotypes would be protected from cancer more effectively by isothiocyanates than those with competent GST enzymes, because the isothiocyanates would be less effectively metabolized and excreted as their conjugates. Some support for this hypothesis has been obtained (37), but one study demonstrated no effect of GSTT1 or GSTM1 status on isothiocyanate excretion after consumption of watercress juice (38,39). …”