Cocoa procyanidins inhibit proliferation and angiogenic signals in human dermal microvascular endothelial cells following stimulation by low-level H2O2.
Date Published: Wednesday, September 1, 2004
Exp Biol Med (Maywood) 2004, 229 (8), 765-71.
Authors: Kenny, T. P.; Keen, C. L.; Jones, P.; Kung, H. J.; Schmitz, H. H.; Gershwin, M. E.
Procyanidins extracted from cocoa play a role in the defense against oxidative stress, as well as in vascular and immune functions. We previously reported that pentameric procyanidins isolated fromcocoa inhibit the expression of the tyrosine kinase ErbB2 gene, thus slowing the growth of culturedhuman aortic endothelial cells. We herein investigate the further consequences of such inhibition bycocoa procyanidins, particularly regarding the protein level in phosphorylation patterns and the effects on the proliferation of human dermal microvascular endothelial cells (HDMECs) followingangiogenic stimulation with low-level H2O2. We report herein that both the pentameric and octameric procyanidin fractions of cocoa inhibit the proliferation of HDMECs, whereas the pentameric fraction modulates the activity of several crucial proteins in angiogenic signaling by altering their tyrosine phosphorylation. Similar to aortic endothelial cells, the pentameric procyanidin fraction down-regulates the expression of ErbB2 tyrosine kinase in HDMECs. In conclusion, we report evidence suggesting that polyphenols may influence endothelial growth signaling, thus affecting angiogenesis in vitro. If these observations are applicable in vivo, they suggest a beneficial effect for cellsoverexpressing ErbB2, such as in specific neoplasias