Binding of Resveratrol to Vascular Endothelial Growth\nFactor Suppresses Angiogenesis by Inhibiting the Receptor Signaling

Resveratrol is a polyphenol commonly\nfound in plants and food health\nproducts, such as grape and red wine, and was identified for its binding\nto vascular endothelial growth factor (VEGF) by using HerboChips screening.\nThe binding, therefore, resulted in alterations of VEGF binding to\nits receptor and revealed the roles of VEGF in angiogenesis. Several\nlines of evidence gave support to the inhibitory activities of resveratrol\nin VEGF-triggered angiogenesis. In human umbilical vein endothelial\ncells (HUVECs), compared with a VEGF-induced group, resveratrol, at\na high concentration, suppressed VEGF-mediated endothelial cell proliferation,\ncell migration, cell invasion, and tube formation by 80 ± 9.01%,\n140 ± 3.78%, 110 ± 7.51%, and 120 ± 10.26%, respectively.\nMoreover, resveratrol inhibited the subintestinal vessel formation\nin zebrafish embryo. In signaling cascades, application of resveratrol\nin HUVECs reduced the VEGF-triggered VEGF receptor 2 phosphorylation\nand c-Jun N-terminal kinase phosphorylation. Moreover, the VEGF-mediated\nphosphorylations of endothelial nitric oxide synthase, protein kinase\nB, and extracellular signal-regulated kinase were obviously decreased\nby (3 ± 0.37)-, (2 ± 0.27)- and (6 ± 0.23)-fold, respectively,\nin the presence of resveratrol at high concentration. Parallelly,\nthe VEGF-induced reactive oxygen species formation was significantly\ndecreased by 50 ± 7.88% to 120 ± 14.82% under resveratrol\ntreatment. Thus, our results provided support to the antiangiogenic\nroles of resveratrol, as well as its related signaling mechanisms,\nin attenuating the VEGF-mediated responses. The present results supported\npossible development of resveratrol, which should be considered as\na therapeutic agent in terms of prevention and clinical treatment\nof diseases related to angiogenesis.