The selectivity and impact of polyphenols-protein kinases interactions for chemoprevention

Phosphorylation of target proteins by protein kinases leads to the activation of cellular signaling pathways, which induce a great number of biological processes including cell growth, differentiation, development, and death. Although the activities of protein kinases are stringently regulated in homeostasis system, protein kinases can be deregulated under pathological conditions, leading to perturbation of protein kinase-mediated cell signaling pathways and resulting in various disorders including cancer, diabetes, and inflammation. The data from the Human Genome Project has revealed that 518 protein kinases are encoded in the human genome, thereby creating an enormous repertoire of potential targets for chemoprevention. Polyphenols, as integral constituents of the diet, have been proposed to exert beneficial effects in a multitude of disease states. Recent studies have suggested that the cellular effects of polyphenols are, at least partly, mediated by their interactions with protein kinases central to intracellular signaling cascades. In the present study, we investigated the interaction of polyphenols-protein kinases by pull down assay, affinity assay and computer simulation. The results revealed that some polyphenols compounds suppressed the phosphorylation of various protein kinases with different affinity and selectivity. Finally, we discussed the impact of these polyphenols-protein kinases interactions on cellular signaling and chemoprevention.