Molecular analysis on the chemopreventive properties of resveratrol, a plant polyphenol microcomponent.

As a plant microcomponent, resveratrol is a polyphenolic compound produced by several species and found especially in Polygonum roots, peanuts seeds, berries and also grape and therefore can be present in human diet or beverages (red wine, for instance). Traditional chinese medicine and more recent epidemiological studies strongly suggested that resveratrol may act as a cancer chemopreventive compound. The biochemical mechanism by which resveratrol inhibits cell proliferation was provided by studies in numerous human cell lines including our work in hepatoblastoma HepG2 and colorectal tumor SW480 cells. The results show that resveratrol strongly inhibits cell proliferation at the micromolar…

PPARs as physiological sensors of fatty acid metabolism molecular regulation in peroxisomes

Transport of resveratrol, a cancer chemopreventive agent, to cellular targets: plasmatic protein binding and cell uptake

Resveratrol produced by several plants, berries and fruits, including grapes, is one of the best known natural food microcomponents with potent chemopreventive properties towards the most severe contemporary human diseases: cardiovascular sickness, cancer and neurodegenerative pathologies. Demonstration of its mechanism of action also implies the elucidation of the steps of bioavailability and bioabsorption in cells and tissues. In order to estimate the relationships between the amounts of resveratrol taken up by food or drink intake, and the several possible benefits illustrated from in vitro/in vivo experiments and from epidemiological studies, it is essential to demonstrate step by step …

Inhibition of hepatic derived cells proliferation by resveratrol

Peroxisome-proliferator-activated receptors as physiological sensors of fatty acid metabolism: molecular regulation in peroxisomes

The enzymes required for the beta-oxidation of fatty acyl-CoA are present in peroxisomes and mitochondria. Administration of hypolipidaemic compounds such as clofibrate to rodents leads to an increase in the volume and density of peroxisomes in liver cells. These proliferators also induce simultaneously the expression of genes encoding acyl-CoA oxidase, enoyl-CoA hydratase-hydroxyacyl-CoA dehydrogenase (multifunctional enzyme) and thiolase (3-ketoacyl-CoA thiolase). All these enzymes are responsible for long-chain and very-long-chain fatty acid beta-oxidation in peroxisomes. Similar results were observed when rat hepatocytes, or liver-derived cell lines, were cultured with a peroxisome prol…

Regulation of the peroxisomal β-oxidation-dependent pathway by peroxisome proliferator-activated receptor α and kinases

The first PPAR (peroxisome proliferator-activated receptor) was cloned in 1990 by Issemann and Green (Nature 347:645-650). This nuclear receptor was so named since it is activated by peroxisome proliferators including several drugs of the fibrate family, plasticizers, and herbicides. This receptor belongs to the steroid receptor superfamily. After activation by a specific ligand, it binds to a DNA response element, PPRE (peroxisome proliferator response element), which is a DR-1 direct repeat of the consensus sequence TGACCT x TGACCT. This mechanism leads to the transcriptional activation of target genes (Motojima et al., J Biol Chem 273:16710-16714, 1998). After the first discovery, severa…