title: Apple procyanidins affect several members of the ErbB receptor tyrosine kinase family in vitro.
abstract: Complex polyphenol-rich extracts from apples are known to inhibit the activity of the epidermal growth factor receptor (EGFR) in vitro. The aim of the present study was to identify the bioactive constituents of the apple juice extract which contribute substantially to this potentially chemopreventive effect and to address the question whether the effect is specific to the EGFR or whether other members of the ErbB-receptor family might also be affected. Apple-derived dihydrochalcones and their respective glycosides were found to decrease EGFR activity under cell-free conditions with IC50-values ranging from 0.4 ± 0.1 to 267.0 ± 50.0 μM but showed no activity on human cancer cells. The concentration of quercetin or its glycosides in the extract was too low to contribute substantially to the EGFR-inhibitory properties. In contrast, fractions derived from the apple juice extract comprising ≥86% oligomeric procyanidins (OPCs) suppressed the activity of the EGFR in cell culture with an IC50 ∼ 100 μg mL(-1). In addition, the activity of further members of the ErbB-receptor family was potently inhibited, with ErbB3 receptor activity being most potently decreased (IC50 ∼ 10 μg mL(-1)). From the apple polyphenols identified so far OPCs were found to add the highest contribution to the inhibitory effects towards members of the ErbB-receptor family. Considering the crucial role of the ErbB-receptors in carcinogenesis, these results support the hypothesis that apple-derived OPCs as well as OPC-rich apple preparations might be of interest with respect to chemoprevention.
authors: Department of Food Chemistry and Toxicology, University of Vienna, Waehringer Strasse 38, 1090 Vienna, Austria.
authors: Nicole
authors: N
authors: Teller
authors: Matthias
authors: M
authors: Roth
authors: Melanie
authors: M
authors: Esselen
authors: Diana
authors: D
authors: Fridrich
authors: Ute
authors: U
authors: Boettler
authors: Volker
authors: V
authors: Blust
authors: Frank
authors: F
authors: Will
authors: Helmut
authors: H
authors: Dietrich
authors: Francis
authors: F
authors: Raul
authors: Wolfgang
authors: W
authors: Hümmer
authors: Elke
authors: E
authors: Richling
authors: Peter
authors: P
authors: Schreier
authors: Doris
authors: D
authors: Marko
mesh_terms: D001628:Beverages / Q000032:analysis*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D020128:Inhibitory Concentration 50; D027845:Malus / Q000737:chemistry*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D059808:Polyphenols / Q000494:pharmacology; D044945:Proanthocyanidins / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D066246:ErbB Receptors; D006861:Hydrogen Peroxide; D010936:Plant Extracts; D059808:Polyphenols; D044945:Proanthocyanidins; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human