The grape-derived polyphenol resveratrol differentially affects epidermal and platelet-derived growth factor signaling in human liver myofibroblasts
Section snippets
Materials
Culture medium, additives and recombinant human EGF and PDGF-BB were from Invitrogen (Life Technologies, Cergy-Pontoise, France). Human AB serum was from Etablissement Français du Sang (Bordeaux, France). Polyvinylidene difluoride membranes were from Millipore (Saint-Quentin en Yvelines, France). Chemicals were from Sigma–Aldrich (Saint-Quentin Fallavier, France). Hyperfilm and the ECL kit were from Amersham (Les Ulis, France). [3H] thymidine was from ICN Biomedicals (Orsay, France).
Resveratrol
Effect of resveratrol on EGF- and PDGF-BB-dependent DNA synthesis
As expected, stimulation with EGF caused a two-fold increase in [3H]thymidine incorporation. Treatment with resveratrol resulted in a dose-dependent inhibition of EGF-induced [3H]thymidine incorporation with an IC50 value of 26.0 ± 1.4 μM (Fig. 1A). Results were normalized with those of a MTT assay conducted in replicate wells; it should be stressed that the MTT results did not differ significantly in any condition (not shown), in agreement with our extensive previous results showing that
Discussion
In a previous study, we have reported that resveratrol was anti-proliferative for human liver myofibroblasts grown in the presence of serum (Godichaud et al., 2000). Here, we show that resveratrol inhibits DNA synthesis when stimulated by EGF or PDGF-BB. As previously described, this was not accompanied by any cytotoxicity (Godichaud et al., 2000). In order to find the target of the anti-proliferative effect of resveratrol, we first examined the effect of resveratrol on growth factor receptor
Acknowledgments
The study was supported in part by grants from Institut de Recherches sur les Boissons and Institut Vin et Santé. SG was the recipient of a fellowship from Berkem Chimie Fine, Gardonne, France.
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