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Vineatrol (R) 30 (developed and produced jointly by Breko GmbH [Bremen, Germany] and Actichem [Montauban, France]) is a grapevine-shoot extract that contains resveratrol as well as considerable amounts of resveratrol oligomers. In the present study it is shown that Vineatrol30 at a noncytotoxic concentration of 2.3 mu g/mL significantly reduced the number of malignantly transformed foci induced by a sequential treatment of BALB/c-3T3 cells with 3-methylcholanthrene and 12-O-tetradecanoylphorbol 13-acetate in the so-called BALB/c-3T3 cell transformation assay. At a higher concentration Vineatrol30 drastically decreased the relative plating efficiency of the cells. Furthermore, the results suggest that the resveratrol oligomers present in Vineatrol30, independently from resveratrol itself, were indeed able to inhibit the formation of malignantly transformed BALB/c-3T3 foci.
The health promoting effects of a grapevine-shoot extract named Vineatrol (R) 30, which contains resveratrol (Resv) as well as considerable amounts of Resv oligomers, have recently been investigated. In the present study, we analyzed the free radical scavenging capacity, the ability to inhibit lipid peroxidation, and the capacity to enhance the human glutathione peroxidase 1 (GPx) and the human superoxide dismutase 1 (SOD) gene promoter activities of Vineatrol (R) 30. Vineatrol (R) 30 was able to scavenge the 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid radical cation and led to concentration-dependent inhibition of lipid peroxidation, Vineatrol (R) 30 not being superior to Resv alone in both cases. Vineatrol (R) 30 also enhanced the gene promoter activities of human GPx and SOD expressed in V79 cells, whereas this effect could not be demonstrated for Resv. In summary, the results presented in this study show that the Vineatrol (R) 30 grapevine-shoot extract is a free radical scavenger and potent antioxidant at non- eytotoxic concentrations.
Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HCAs) ingested with food have repeatedly been suggested to be involved in the malignant transformation of colon epithelial cells. In order to test this hypothesis, HCEC cells (SV40 large T antigen-immortalized human colon epithelial cells) were incubated with a racemic mixture of benzo[c]phenanthrene dihydrodiol epoxides (B[c]PhDE), extremely potent carcinogenic PAH metabolites in vivo, or with 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP), the N-hydroxylated metabolite of the most abundant HCA in cooked meat. First, it was shown that HCEC cells express sulfotransferase 1A1, which is needed to metabolize N-OH-PhIP to the corresponding N-sulfonyloxy derivative, the direct precursor molecule of genotoxic nitrenium ions. Thereafter, exponentially growing HCEC cells were exposed five times to 0.1 mu g (0.37 nmol) B[c]PhDE/ml for 30 min or 0.72 mu g (3 mnol) N-OH-PhTP/ml for 24 h. Chemically treated HCEC cells showed an enhanced saturation density and grew faster than the corresponding solvent-treated cell cultures. After five treatment cycles, HCECB[c]PhDE as well as HCECN-OH-PhIP cells lost cell-cell contact inhibition and started piling up and forming foci in the culture flasks. Furthermore, HCECB[c]phDE and HCECN-OH-PhIP cells were injected i.m. into SCID mice. Within 6 weeks after injection, eight animals out of eight injected with HCECB[c]phDE or HCECN-OH-PhIP cells developed tumors at the site of injection, thus demonstrating the high tumorigenic potential of the HCECB[c]PhDE and HCECN-OH-PhIP cell cultures. Taken together, we show for the first time that the abovementioned active PAH metabolites as well as N-OH-PhIP are indeed able to malignantly transform human colon epithelial cells in vitro.