While a number of dietary polyphenolic compounds have
been shown to inhibit VEGF-induced VEGFR-2 phosphorylation
[16], the underlying molecular mechanisms are not
known. Polyphenols may inhibit VEGF-induced VEGFR-2
phosphorylation in three ways: (i) by binding directly to the
VEGF molecule in a way that prevents VEGF from binding
to its receptor; (ii) by binding to the VEGF receptor in a way
that prevents VEGF from binding and/or activating the receptor;
or (iii) by interacting with intracellular components
involved in phosphorylation of VEGFR-2. The original aim
of the present study was to determine whether polyphenols
interact with the VEGF ligand or with components of the
endothelial cells (VEGFR-2, intracellular kinases, etc.) to inhibit
VEGFR-2 activation. We present data which show that
epigallocatechin gallate (EGCG) and procyanidin oligomers
inhibit VEGF-mediated VEGFR-2 phosphorylation by directly
interacting with VEGF and reducing its binding to the receptor.
We also report some interesting features of the binding
between the polyphenols and VEGF and data on the downstream
effects of polyphenol-mediated inhibition of VEGFR-2
activation.