Current address: Nutrición y Bromatología Facultad de Farmacia Universidad de Sevilla, C/ Profesor García González, Sevilla 41012, España
Potent inhibition of VEGFR-2 activation by tight binding of green tea epigallocatechin gallate and apple procyanidins to VEGF: Relevance to angiogenesis
Version of Record online: 22 JAN 2015
© 2014 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Molecular Nutrition & Food Research
Volume 59, Issue 3, pages 401–412, March 2015
How to Cite
Moyle, C. W. A., Cerezo, A. B., Winterbone, M. S., Hollands, W. J., Alexeev, Y., Needs, P. W. and Kroon, P. A. (2015), Potent inhibition of VEGFR-2 activation by tight binding of green tea epigallocatechin gallate and apple procyanidins to VEGF: Relevance to angiogenesis. Mol. Nutr. Food Res., 59: 401–412. doi: 10.1002/mnfr.201400478
- Issue online: 3 MAR 2015
- Version of Record online: 22 JAN 2015
- Accepted manuscript online: 25 DEC 2014 06:51AM EST
- Manuscript Accepted: 15 DEC 2014
- Manuscript Revised: 14 OCT 2014
- Manuscript Received: 17 JUL 2014
- Dietary polyphenols;
- Nitric oxide synthase;
Excessive concentrations of vascular endothelial growth factor (VEGF) drive angiogenesis and cause complications such as increased growth of tumours and atherosclerotic plaques. The aim of this study was to determine the molecular mechanism underlying the potent inhibition of VEGF signalling by polyphenols.
Methods and results
We show that the polyphenols epigallocatechin gallate from green tea and procyanidin oligomers from apples potently inhibit VEGF-induced VEGF receptor-2 (VEGFR-2) signalling in human umbilical vein endothelial cells by directly interacting with VEGF. The polyphenol-induced inhibition of VEGF-induced VEGFR-2 activation occurred at nanomolar polyphenol concentrations and followed bi-phasic inhibition kinetics. VEGF activity could not be recovered by dialysing VEGF-polyphenol complexes. Exposure of VEGF to epigallocatechin gallate or procyanidin oligomers strongly inhibited subsequent binding of VEGF to human umbilical vein endothelial cells expressing VEGFR-2. Remarkably, even though VEGFR-2 signalling was completely inhibited at 1 μM concentrations of polyphenols, endothelial nitric oxide synthase was shown to still be activated via the PI3K/Akt signalling pathway which is downstream of VEGFR-2.
These data demonstrate for the first time that VEGF is a key molecular target for specific polyphenols found in tea, apples and cocoa which potently inhibit VEGF signalling and angiogenesis at physiological concentrations. These data provide a plausible mechanism which links bioactive compounds in food with their beneficial effects.