Zeaxanthin inhibits PDGF-BB-induced migration in human dermal fibroblasts

Zeaxanthin is the dihydroxy carotenoid and is distributed in our daily foods. Various natural carotenoids, including zeaxanthin, have been shown to inhibit proliferation of several types of cancer cells, but available data on the effect of zeaxanthin on skin fibroblasts and melanoma cells are limited. Platelet-derived growth factor (PDGF) functions as a chemotactic factor for dermal fibroblasts and plays an important role in the progression of melanoma. In this study, we investigated the effects of zeaxanthin on the migration of skin fibroblasts induced by PDGF-BB and melanoma cells. We demonstrated that zeaxanthin inhibited PDGF-BB-induced skin fibroblast migration on collagen and gelatin by a modified Boyden chamber system. The electric cell-substrate impedance sensing (ECIS) method also showed similar inhibitory effects of zeaxanthin on the migration of fibroblasts. In functional studies, zeaxanthin decreased melanoma-induced fibroblast migration in a non-contact coculture system and also the migration stimulated by melanoma-derived conditioned medium. Further analysis showed that zeaxanthin attenuated PDGF-BB and melanoma-conditioned medium induced phosphorylation of PDGFR-beta and MAP kinase in a concentration-dependent manner in human skin fibroblasts. However, these effects did not result from direct interaction of zeaxanthin with PDGF-BB. Thus, our results provide the first evidence showing that zeaxanthin is an effective inhibitor of migration of stromal fibroblasts induced by PDGF-BB and melanoma cells and this effect may further support its antitumor potential.