Modulation of detoxification enzymes by watercress: in vitro and in vivo investigations in human peripheral blood cells.
BACKGROUND
Epidemiological studies indicate that consumption of cruciferous vegetables (CV) can reduce the risk of cancer. Supposed mechanisms are partly the inhibition of phase I and the induction of phase II enzymes.


OBJECTIVE
The aim of this study was to investigate in vitro and in vivo effects of watercress (WC), a member of the CV family, on chemopreventive parameters using human peripheral blood mononuclear cells (PBMC) as surrogate cells. We investigated the hypothesis that WC reduces cancer risk by inducing detoxification enzymes in a genotype-dependent manner.


METHODS
In vitro gene expression and enzyme activity experiments used PBMC incubated with a crude extract from fresh watercress (WCE, 0.1-10 microL/mL with 8.2 g WC per 1 mL extract) or with one main key compound phenethyl isothiocyanate (PEITC, 1-10 microM). From an in vivo perspective, gene expression and glutathione S-transferase (GST) polymorphisms were determined in PBMC obtained from a human intervention study in which subjects consumed 85 g WC per day for 8 weeks. The influence of WC consumption on gene expression was determined for detoxification enzymes such as superoxide dismutase 2 (SOD2) and glutathione peroxidase 1 (GPX1), whilst the SOD and GPX activities in red blood cells were also analysed with respect to GST genotypes.


RESULTS
In vitro exposure of PBMC to WCE or PEITC (24 h) increased gene expression for both detoxification enzymes GPX1 (5.5-fold, 1 microL/mL WCE, 3.7-fold 1 microM PEITC) and SOD2 (12.1-fold, 10 microL/mL WCE, 7.3-fold, 10 microM PEITC), and increased SOD2 activity (1.9-fold, 10 microL/mL WCE). The WC intervention had no significant effect on in vivo PBMC gene expression, as high individual variations were observed. However, a small but significant increase in GPX (p = 0.025) and SOD enzyme activity (p = 0.054) in red blood cells was observed in GSTM1*0, but not in GSTM1*1 individuals, whilst the GSTT1 genotype had no impact.


CONCLUSIONS
The results indicate that WC is able to modulate the enzymes SOD and GPX in blood cells in vitro and in vivo, and suggest that the capacity of moderate intake of CV to induce detoxification is dependent in part on the GSTM1 genotype.
Hofmann
Thomas
T
Department of Nutritional Toxicology, Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Str. 24, 07743, Jena, Germany. th.hofmann@gmail.com
Kuhnert
A
A
Schubert
A
A
Gill
C
C
Rowland
I R
IR
Pool-Zobel
B L
BL
Glei
M
M
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D005838:Genotype; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D031223:Nasturtium / Q000737:chemistry*; D009369:Neoplasms / Q000517:prevention & control*; D010936:Plant Extracts / Q000494:pharmacology*; D011110:Polymorphism, Genetic; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000094765:Glutathione Peroxidase GPX1; D000099156:Superoxide Dismutase 2
D016588:Anticarcinogenic Agents; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D017879:Isothiocyanates; D010936:Plant Extracts; D013482:Superoxide Dismutase; D000094765:Glutathione Peroxidase GPX1; D000099156:Superoxide Dismutase 2; C058305:phenethyl isothiocyanate