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Drug development targeting the glycogen synthase kinase-3beta (GSK-3beta)-mediated signal transduction pathway: inhibitors of the Wnt/beta-catenin signaling pathway as novel anticancer drugs Takahashi-Yanaga F; Sasaguri TJ Pharmacol Sci 2009[Feb]; 109 (2): 179-83Accumulating evidence suggests that the Wnt/beta-catenin signaling pathway is often involved in oncogenesis and cancer development. Accordingly, a novel anticancer drug can be developed using inhibitors of this pathway. However, at present, there is no selective inhibitor of this pathway available as a therapeutic agent. Although all the components of the Wnt/beta-catenin signaling pathway can be a target for drug development, glycogen synthase kinase-3beta (GSK-3beta), in particular, may be a good target because GSK-3beta is an essential component of the pathway, and activation of this kinase results in the inhibition of the Wnt signaling pathway. We found that the differentiation-inducing factors (DIFs), putative morphogens for Dictyostelium discoideum, inhibit the Wnt/beta-catenin signaling pathway via the activation of GSK-3beta, resulting in the cell-cycle arrest of human cancer cell lines. In this review, we summarize our recent findings on the antiproliferative effect of DIFs and show the possibility for development of a novel anticancer drug from DIFs and their derivatives.|Animals[MESH]|Antineoplastic Agents/*pharmacology[MESH]|Cyclin D1/metabolism/physiology[MESH]|Drug Delivery Systems[MESH]|Glycogen Synthase Kinase 3 beta[MESH]|Glycogen Synthase Kinase 3/drug effects/metabolism[MESH]|Hexanones/*pharmacology[MESH]|Humans[MESH]|Hydrocarbons, Chlorinated/*pharmacology[MESH]|Mice[MESH]|Signal Transduction[MESH]|Wnt Proteins/*antagonists & inhibitors[MESH]|beta Catenin/*antagonists & inhibitors[MESH] |
