Document Detail


Pentameric procyanidins isolated from Theobroma cacao seeds selectively downregulate ErbB2 in human aortic endothelial cells.
MedLine Citation:
PMID:  14988518     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Flavonoids isolated from cocoa have biological activities relevant to oxidant defenses, vascular health, tumor suppression, and immune function. The intake of certain dietary flavonoids, along with other dietary substances such as tocopherols, ascorbate, and carotenoids, is epidemiologically associated with a reduced risk of cardiovascular disease. Flavonoids have also been shown to modulate tumor pathology in vitro and in animal models. We took advantage of the conserved sequences found in tyrosine kinases to study the influence of cocoa fractions and controls on gene expression. We report that the pentameric procyanidin (molecular weight of 1442 daltons) fraction isolated from cocoa was a potent inhibitor of tyrosine kinase ErbB2 expression, a receptor important in angiogenesis regulation. Consistent with this primary observation, the cocoa flavonoid fraction also suppressed human aortic endothelial cell (HAEC) growth and decreased expression of two tyrosine kinases responsive to ErbB2 modulation, namely VEGFR-2/KDR and MapK 11/p38beta2. These inhibitory effects were observed when HAECs were treated with the flavonol fraction (molecular weight 280 daltons) isolated from cocoa, which comprise the structural subunits from which the procyanidin flavonoid subclass is biosynthetically constructed. Down-regulation of ErbB2 and inhibition of HAEC growth by cocoa procyanidins may have several downstream implications, including reduced vascular endothelial growth factor (VEGF) activity and angiogenic activity associated with tumor pathology. These results suggest specific dietary flavonoids are capable of selectively inhibiting ErbB2 and therefore may offer important insight into the design of therapeutic agents that target tumors overexpressing ErbB2.
Authors:
Thomas P Kenny; Carl L Keen; Paul Jones; Hsing-Jien Kung; Harold H Schmitz; M Eric Gershwin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental biology and medicine (Maywood, N.J.)     Volume:  229     ISSN:  1535-3702     ISO Abbreviation:  Exp. Biol. Med. (Maywood)     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-02-27     Completed Date:  2004-03-24     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  100973463     Medline TA:  Exp Biol Med (Maywood)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  255-63     Citation Subset:  IM    
Affiliation:
Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, California 95616, USA.
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MeSH Terms
Descriptor/Qualifier:
Antioxidants / pharmacology*
Aorta / drug effects
Biflavonoids*
Cacao*
Catechin / pharmacology*
Cell Division / drug effects
Endothelial Cells / drug effects*
Gene Expression / drug effects
Humans
Mitogen-Activated Protein Kinase 11
Mitogen-Activated Protein Kinases / biosynthesis,  drug effects
Plant Extracts / pharmacology
Proanthocyanidins*
Receptor, erbB-2 / drug effects*
Reverse Transcriptase Polymerase Chain Reaction
Vascular Endothelial Growth Factor Receptor-2 / biosynthesis,  drug effects
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Biflavonoids; 0/Plant Extracts; 0/Proanthocyanidins; 154-23-4/Catechin; 4852-22-6/procyanidin; EC 2.7.10.1/Receptor, erbB-2; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-2; EC 2.7.11.24/Mitogen-Activated Protein Kinase 11; EC 2.7.11.24/Mitogen-Activated Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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