The role of dynamin in actin dynamics: Development of anticancer drugs inhibiting dynamin function

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In search of more effective inhibitor for dynamin than dynasore, one hundred eighty one dynasore analogues were screened by in vitro actin polymerization assay. N'-(4-(diethylamino)benzylidene)-4-methoxybenzohydrazide (DBHA) was identified as a potent dynamin inhibitor. DBHA strongly inhibited the serum-stimulated ruffle formation, cell migration and invasion. Under these conditions, DBHA showed little toxicity for cultured cancer cell line. Furthermore, we clarified the function of dynamin/cortactin complex in the regulation of actin dynamics. The dynamin/cortactin complexes bundled several actin filaments and the bundling stabilized actin filaments. The actin bundling by dynamin/cortactin complex was necessary for formation of growth cone filopodia and cell migration. These findings might be crucial for developping anti cancer drugs.