Inhibitors of the epidermal growth factor receptor in apple juice extract.
The polyphenol-rich extract of a consumer-relevant apple juice blend was found to potently inhibit the growth of the human colon cancer cell line HT29 in vitro. The epidermal growth factor receptor (EGFR) and its subsequent signaling cascade play an important role in the regulation of cell proliferation in HT29 cells. The protein tyrosine kinase activity of an EGFR preparation was effectively inhibited by the polyphenol-rich apple juice extract. Treatment of intact cells with this extract resulted in the suppression of the subsequent mitogen-activated protein kinase cascade. Amongst the so far identified apple juice constituents, the proanthocyanidins B1 and B2 as well as quercetin-3-glc (isoquercitrin) and quercetin-3-gal (hyperoside) were found to possess substantial EGFR-inhibitory properties. However, as to be expected from the final concentration of these potential EGFR inhibitors in the original polyphenol-rich extract, a synthetic mixture of the apple juice constituents identified and available so far, including both proanthocyanidins and the quercetin glycosides, showed only marginal inhibitory effects on the EGFR. These results permit the assumption that yet unknown constituents contribute substantially to the potent EGFR-inhibitory properties of polyphenol-rich apple juice extract. In summary, the polyphenol composition of apple juice possesses promising growth-inhibitory properties, affecting proliferation-associated signaling cascades in colon tumor cells.
Kern
Melanie
M
Department of Chemistry, Division of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Kaiserslautern, Germany.
Tjaden
Zeina
Z
Ngiewih
Yufanyi
Y
Puppel
Nicole
N
Will
Frank
F
Dietrich
Helmut
H
Pahlke
Gudrun
G
Marko
Doris
D
D001628:Beverages / Q000032:analysis*; D002109:Caffeic Acids / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D005419:Flavonoids / Q000032:analysis / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D008156:Luciferases / Q000235:genetics; D027845:Malus / Q000737:chemistry*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D010636:Phenols / Q000032:analysis / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D059808:Polyphenols; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D014846:Vulvar Neoplasms; D050807:ets-Domain Protein Elk-1
D002109:Caffeic Acids; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; C052130:GAL4 protein, S cerevisiae; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D008156:Luciferases; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases; C040048:caffeic acid