Perturbation of the EphA2鈥揈phrinA1 System in Human Prostate Cancer Cells by Colonic (Poly)phenol Catabolites
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- 作者：Massimiliano Tognolini ; Carmine Giorgio ; Iftiin Hassan Mohamed ; Elisabetta Barocelli ; Luca Calani ; Eric Reynaud ; Olivier Dangles ; Gina Borges ; Alan Crozier ; Furio Brighenti ; Daniele Del Rio
- 刊名：Journal of Agricultural and Food Chemistry
- 出版年：2012
- 出版时间：September 12, 2012
- 年：2012
- 卷：60
- 期：36
- 页码：8877-8884
- 全文大小：323K
- 年卷期：v.60,no.36(September 12, 2012)
- ISSN：1520-5118
文摘
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鈥揺phrinA1 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 (IC50 values from 0.26 to 43 渭M). 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.