Apple polyphenols diminish the phosphorylation of the epidermal growth factor receptor in HT29 colon carcinoma cells.
Previously, we showed that an apple juice extract (AE) potently inhibits the protein tyrosine kinase (PTK) activity of the epidermal growth factor receptor (EGFR). In the present study, an apple pomace extract (APE) was found to exceed the EGFR inhibitory properties of AE in a cell-free system. The impact of the extracts on the phosphorylation status of the EGFR in intact cells (HT29) was sensitive to catalase, added to suppress the accumulation of hydrogen peroxide. In the absence of catalase, the formation of hydrogen peroxide was observed, achieving 1.1 +/- 0.1 microM (AE) and 1.5 +/- 0.1 microM (APE) after 45 min of incubation. In the presence of catalase, suppressing the hydrogen peroxide level to the solvent control, APE effectively suppressed EGFR phosphorylation, even exceeding the effects of AE. Both extracts inhibited the growth of HT29 cells, albeit the enhanced EGFR inhibitory properties of APE compared to AE were not reflected by a higher growth inhibitory potential. The results clearly show that the effect of apple extracts on the EGFR and cell growth are not simply artefacts of hydrogen peroxide formation. However, the formation of hydrogen peroxide has to be considered to modulate and/or mask cellular responses to apple extracts.
Fridrich
Diana
D
Institute of Applied Biosciences, Section of Food Toxicology, University of Karlsruhe TH, Karlsruhe, Germany.
Kern
Melanie
M
Pahlke
Gudrun
G
Volz
Nadine
N
Will
Frank
F
Dietrich
Helmut
H
Marko
Doris
D
D002455:Cell Division / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D005638:Fruit / Q000737:chemistry*; D019073:HT29 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D027845:Malus / Q000737:chemistry*; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D059808:Polyphenols; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors
D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D006861:Hydrogen Peroxide; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases