Lycopene binds PDGF-BB and inhibits PDGF-BB-induced intracellular signaling transduction pathway in rat smooth muscle cells

Cardiovascular diseases (CVDs) result from the sub-endothelial accumulation of inflammatory cells and smooth muscle cells (SMCs). Lycopene, a natural compound from tomato, has been suggested to play a role in CVD prevention. However, its action mechanism is still largely unknown. In this study, we examined the effect of lycopene on SMCs. We found that preincubation of PDGF-BB with lycopene resulted in a marked inhibition on PDGF-BB-induced PDGF receptor-beta (PDGFR-beta), PLC-gamma, and ERK1/2 phosphorylation in rat A10 SMCs and primary cultured aortic SMCs. In striking contrast, lycopene did not influence EGF-induced ERK1/2 phosphorylation. Surprisingly, further analysis indicates that lycopene could directly bind PDGF-BB and inhibit PDGF-BB-SMC interaction, as determined by dot binding assay and Western blotting. In functional studies, lycopene inhibited PDGF-BB-induced SMC proliferation and migration toward gelatin and collagen at concentrations ranging from 2 to 10 mu M. On the contrary, lycopene did not inhibit bFGF- and VEGF-induced endothelial cell migration. Gelatin zymography demonstrated that lycopene's effect on SMC migration was not due to the inhibition of matrix metalloproteinases (MMPs). Taken together, our results provide the first evidence showing that lycopene inhibits PDGF-BB-induced signaling, proliferation and migration in rat A10 and aortic SMCs. One of the action mechanisms is that lycopene is capable of binding PDGF-BB and inhibiting its interaction with SMC, which is quite different from those previously developed PDGFR-P antagonists. The results presented here may help us to better understand the beneficial effects of lycopene in CVD prevention. (c) 2007 Elsevier Inc. All rights reserved.