Oak ellagitannins suppress the phosphorylation of the epidermal growth factor receptor in human colon carcinoma cells.
The ellagitannins castalagin and vescalagin, and the C-glycosides grandinin and roburin E as well as ellagic acid were found to potently inhibit the growth of human colon carcinoma cells (HT29) in vitro. In a cell-free system these compounds were identified as potent inhibitors of the protein tyrosine kinase activity of the epidermal growth factor receptor (EGFR) with IC 50 values in the low nanomolar range. To address the question of whether the interference with the activity of the isolated EGFR also plays a role within intact cells, effects on the phosphorylation status of the EGFR, as a measure for its activity, were determined in HT29 cells. As exemplified for castalagin and grandinin, both the nonglycosylated and the glycosylated ellagitannins effectively suppressed EGFR phosphorylation, but only at concentrations > or =10 microM, thus, in a concentration range where growth inhibition was observed. These results indicate that the suppression of EGFR-mediated signaling might contribute to the growth inhibitory effects of these compounds present in oak-matured wines and spirits such as whiskey. In contrast, despite substantial growth inhibitory properties, ellagic acid did not significantly affect EGFR phosphorylation in HT29 cells up to 100 microM.
Fridrich
Diana
D
Lehrstuhl für Lebensmittelchemie and Molekulare Sensorik, Technische Universität München, Lise-Meitner-Strasse 34, D-85354 Freising, Germany.
Glabasnia
Arne
A
Fritz
Jessica
J
Esselen
Melanie
M
Pahlke
Gudrun
G
Hofmann
Thomas
T
Marko
Doris
D
D001713:Biphenyl Compounds / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002474:Cell-Free System; D004791:Enzyme Inhibitors; D066246:ErbB Receptors / Q000378:metabolism*; D006027:Glycosides / Q000494:pharmacology; D006031:Glycosylation; D019073:HT29 Cells; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D029963:Quercus / Q000737:chemistry*
D001713:Biphenyl Compounds; D002396:Catechols; D004791:Enzyme Inhibitors; D006027:Glycosides; D006576:Heterocyclic Compounds, 4 or More Rings; D047348:Hydrolyzable Tannins; C479598:grandinin; C084709:vescalagin; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases