Resveratrol is a polyphenol commonly
found in plants and food health
products, such as grape and red wine, and was identified for its binding
to vascular endothelial growth factor (VEGF) by using HerboChips screening.
The binding, therefore, resulted in alterations of VEGF binding to
its receptor and revealed the roles of VEGF in angiogenesis. Several
lines of evidence gave support to the inhibitory activities of resveratrol
in VEGF-triggered angiogenesis. In human umbilical vein endothelial
cells (HUVECs), compared with a VEGF-induced group, resveratrol, at
a high concentration, suppressed VEGF-mediated endothelial cell proliferation,
cell migration, cell invasion, and tube formation by 80 ± 9.01%,
140 ± 3.78%, 110 ± 7.51%, and 120 ± 10.26%, respectively.
Moreover, resveratrol inhibited the subintestinal vessel formation
in zebrafish embryo. In signaling cascades, application of resveratrol
in HUVECs reduced the VEGF-triggered VEGF receptor 2 phosphorylation
and c-Jun N-terminal kinase phosphorylation. Moreover, the VEGF-mediated
phosphorylations of endothelial nitric oxide synthase, protein kinase
B, and extracellular signal-regulated kinase were obviously decreased
by (3 ± 0.37)-, (2 ± 0.27)- and (6 ± 0.23)-fold, respectively,
in the presence of resveratrol at high concentration. Parallelly,
the VEGF-induced reactive oxygen species formation was significantly
decreased by 50 ± 7.88% to 120 ± 14.82% under resveratrol
treatment. Thus, our results provided support to the antiangiogenic
roles of resveratrol, as well as its related signaling mechanisms,
in attenuating the VEGF-mediated responses. The present results supported
possible development of resveratrol, which should be considered as
a therapeutic agent in terms of prevention and clinical treatment
of diseases related to angiogenesis.
