The Eph tyrosine kinase receptors and their ephrin ligands play a central role in human cancer as their deregulated expression induces tumorigenesis with aggressive phenotypes. To evaluate their potential contribution to EphA2-ephrinA1 modulation, several colonic catabolites of dietary (poly)phenolics, known to be generated in vivo, were screened using an ELISA-based binding assay. Some of the catabolites inhibited the binding in a dose-dependent manner (IC(50) values from 0.26 to 43 μM). Functional studies on prostate adenocarcinoma cells revealed that pyrogallol and protocatechuic acid specifically antagonized ephrinA1-Fc-induced EphA2 phosphorylation at concentrations that were not cytotoxic. The active concentrations of pyrogallol appear to be close to what can be reached in vivo under physiological conditions. Finally, because of the roles played by the Eph-ephrin system not only in cancer development but also in neurodegeneration and diabetes, pyrogallol and protocatechuic acid are candidates for more detailed functional studies to elucidate their role in these pathophysiological processes.
Written by:
Tognolini M, Giorgio C, Hassan Mohamed I, Barocelli E, Calani L, Reynaud E, Dangles O, Borges G, Crozier A, Brighenti F, Del Rio D Are you the author?
Dipartimento di Scienze Farmacologiche, Biologiche e Chimiche Applicate, Università di Parma , Viale delle Scienze 27a, 43124 Parma, Italy.
Reference: J Agric Food Chem. 2012 Mar 21
doi: 10.1021/jf205305m
PubMed Abstract
PMID: 22409255