Publications (37) View all
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Article: Time- and concentration-dependent effects of resveratrol in HL-60 and HepG2 cells.
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ABSTRACT: Resveratrol, a phytochemical present in grapes, has been demonstrated to inhibit tumourigenesis in animal models. However, the specific mechanism by which resveratrol exerts its anticarcinogenic effect has yet to be elucidated. In the present study, the inhibitory effects of resveratrol on cell proliferation and apoptosis were evaluated in the human leukaemia cell line HL-60 and the human hepatoma derived cell line HepG2. We found that after a 2 h incubation period, resveratrol inhibited DNA synthesis in a concentration-dependent manner. The IC50 value was 15 microm in both HL-60 and HepG2 cells. When the time of treatment was extended, an increase in IC50 value was observed; for example, at 24 h the IC50 value was 30 microm for HL-60 cells and 60 microm for HepG2 cells. Flow cytometry revealed that cells accumulated in different phases of the cell cycle depending on the resveratrol concentration. Furthermore, an increase in nuclear size and granularity was observed in the G1 and S phases of HL-60 treated and HepG2-treated cells. Apoptosis was also stimulated by resveratrol in a concentration-dependent manner in HL-60 and HepG2 cells. In conclusion, resveratrol inhibits cell proliferation in a concentration- and time-dependent manner by interfering with different stages of the cell cycle. Furthermore, resveratrol treatment causes stimulation of apoptosis as well as an increase in nuclear size and granularity.Cell Proliferation 01/2007; 39(6):479-93. · 2.52 Impact Factor -
Article: Biochemical effects of dietary intakes of different broccoli samples. I. Differential modulation of cytochrome P-450 activities in rat liver, kidney, and colon.
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ABSTRACT: Modulation of xenobiotic metabolism, including cytochrome P-450 (CYP) enzyme activities, due to dietary intakes of cruciferous vegetables, has been described in animals and humans, and the induction of CYP1A enzymes is suggested mainly to be related to the content of indolyl glucosinolates in these vegetables. The aim of the present study was to evaluate the effects on specific CYP activities of various broccoli samples containing different levels of glucosinolates. Groups of rats were fed 1 of 8 broccoli samples from 2 cultivars grown at different conditions. Thirteen different glucosinolates were quantified. The content of the 4 major glucosinolates, glucoraphanin (GRAP), glucoiberin, glucobrassicin (GB), and neoglucobrassicin (NeoGB) varied 5.6-, 2.7-, 3.2-, and 6.6-fold, respectively, among the broccoli samples. Dietary broccoli induced the CYP1A enzyme activities, 7-ethoxyresorufin-O-deethylase (EROD) and 7-methoxyresorufin-O-demethylase (MROD), in rat liver, weakly in colon, but not in kidney. In concordance, the hepatic metabolism of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) to the proximate carcinogen N-OH-PhIP, a CYP1A-related activity, was enhanced by broccoli. The 7-pentoxyresorufin-O-depenthylase (PROD) activity, an assay for CYP2B1/2, was weakly induced in colon and kidney but not in liver by broccoli. The 2 beta-OH- and 6 beta-OH-testosterone hydroxylase activities were induced in liver microsomes, showing that broccoli increased CYP3A activity. The observed modulations of CYP activities depended clearly on the broccoli sample used, and significantly different responses were observed for different cultivars and growth conditions. These results indicate that modulation of CYP metabolism by broccoli may vary significantly in humans as well, as the content of glucosinolates and other active substances also varies between commercially available broccoli samples. The different effects depending on the vegetable sample eaten have to be considered in future experiments and dietary recommendations.Metabolism 11/2001; 50(10):1123-9. · 2.66 Impact Factor -
Article: Biochemical effects of dietary intake of different broccoli samples. II. Multivariate analysis of contributions of specific glucosinolates in modulating cytochrome P-450 and antioxidant defense enzyme activities.
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ABSTRACT: Dietary broccoli exposure modulates various cytochrome P-450 (CYP)-associated activities and antioxidant defense enzyme activities in liver, colon, and kidney of rats. We present an analysis by the partial least-square method (PLS) of the contribution of single glucosinolates in modulating xenobiotic metabolizing and antioxidant defense enzyme activities. Generally, modulation of colonic enzyme activities was well described (58% to 75%) by models consisting of 3 principal components (PCs). The indolyl glucosinolates were not the only major contributors to the regulation of colonic 7-ethoxyresorufin O-deethylase (EROD) and 7-methoxyresorufin O-demethylase (MROD) activities, as would be expected from results of previous experiments testing the pure compounds, glucobrassicin (GB), neoglucobrassicin (NeoGB), and 4-methoxyglucobrassicin (4-MeOGB). In hepatic and renal microsomes, the modulation of enzyme activities could be partly described for hepatic and renal 7-pentoxyresorufin O-deethylase (PROD) activities (42% to 44%, 3 to 4 PCs), hepatic superoxide dismutase activity (45%, 2 PCs), and renal glutathione peroxidase (GSH Px) and glutathione reductase (GSSG Red) activities (43%, 3 PCs). These results indicate that substances other than glucosinolates in the complex mixtures modulate hepatic EROD, MROD, GSH Px, and GSSG Red activities or that the active glucosinolate metabolites vary in their systemic disposition.Metabolism 11/2001; 50(10):1130-5. · 2.66 Impact Factor -
Article: Functional food ingredients against colorectal cancer. An example project integrating functional genomics, nutrition and health.
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ABSTRACT: Functional Food Ingredients Against Colorectal Cancer is one of the first European Union funded Research Projects at the cross-road of functional genomics [comprising transcriptomics, the measurement of the expression of all messengers RNA (mRNAs) and proteomics, the measurement of expression/state of all proteins], nutrition and human health. The goal of Functional Food Ingredients Against Colorectal Cancer is to develop a colon epithelial cell line-based screening assay for nutrients with presumed anti-colorectal carcinogenic properties. Genes involved in colon carcinogenesis are identified at the RNA and protein level, using a variety of methods (subtractive hybridisation, DNA microarray, proteomics) in combination with models for colorectal cancer development (human biopsies, rat model for colorectal carcinogenesis, colorectal cancer epithelial cell lines). Secondly, colorectal cancer epithelial cell lines are selected, in terms of their capacity to undergo gene/protein expression changes representing different phases in the colorectal carcinogenesis. Thirdly, these cell lines are used to determine the effects of nutrients with presumed anti-carcinogenic properties (e.g. resveratrol, flavonoids) on functional genomics-derived endpoints. Once validated against the effects of these nutrients in in vivo animal models and classical biomarkers for colorectal carcinogenesis, these cell line models combined with functional genomics represent useful tools to study colorectal carcinogenesis and screen for nutrients with anti-carcinogenic properties.Nutrition Metabolism and Cardiovascular Diseases 09/2001; 11(4 Suppl):94-8. · 3.73 Impact Factor -
Article: Resveratrol reverses tumor-promoter-induced inhibition of gap-junctional intercellular communication.
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ABSTRACT: The naturally occurring stilbene/alexin trans-resveratrol (trans-3,5, 4'-trihydroxystilbene) is a promising agent for the prevention of cancer. We investigated the effect of resveratrol on gap-junctional intercellular communication (GJIC) in WB-F344 rat liver epithelial cells because inhibition of GJIC is an important mechanism of tumor promotion. Seventeen to 50 microM resveratrol increased GJIC significantly by a factor of 1.3 compared with solvent vehicle controls, when the WB-F344 cells were exposed to resveratrol for 6 h. Most tumor promoters, including the phorbol ester TPA and the insecticide DDT, block GJIC. Resveratrol at 17-50 microM also significantly prevented down-regulation of GJIC by TPA and DDT, by a factor of 2.7 and 1.8, respectively. This recovery of GJIC from TPA inhibition was partly correlated with hindered hyperphosphorylation of Cx43. In conclusion, resveratrol was found to enhance GJIC and counteract the effects of tumor promoters on GJIC, and this is likely a mechanism that contributes to the antipromotional and anticarcinogenic properties of resveratrol.Biochemical and Biophysical Research Communications 10/2000; 275(3):804-9. · 2.48 Impact Factor
