title: Perturbation of the EphA2-EphrinA1 system in human prostate cancer cells by colonic (poly)phenol catabolites.
abstract: 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.
authors.affiliation: Dipartimento di Scienze Farmacologiche, Biologiche e Chimiche Applicate,  Università di Parma , Viale delle Scienze 27a, 43124 Parma, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Tognolini
authors.forename: Carmine
authors.initials: C
authors.lastname: Giorgio
authors.forename: Iftiin
authors.initials: I
authors.lastname: Hassan Mohamed
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Barocelli
authors.forename: Luca
authors.initials: L
authors.lastname: Calani
authors.forename: Eric
authors.initials: E
authors.lastname: Reynaud
authors.forename: Olivier
authors.initials: O
authors.lastname: Dangles
authors.forename: Gina
authors.initials: G
authors.lastname: Borges
authors.forename: Alan
authors.initials: A
authors.lastname: Crozier
authors.forename: Furio
authors.initials: F
authors.lastname: Brighenti
authors.forename: Daniele
authors.initials: D
authors.lastname: Del Rio
mesh_terms: D045744:Cell Line, Tumor; D003106:Colon / Q000378:metabolism*; D036382:Ephrin-A1 / Q000378:metabolism*; D006801:Humans; D008297:Male; D059808:Polyphenols / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D036104:Receptor, EphA2 / Q000378:metabolism*
chemical_list: D036382:Ephrin-A1; D059808:Polyphenols; D036104:Receptor, EphA2