Chalcones are precursors of flavonoids and have been shown to have anti-cancer activity Here, we identify the synthetic chalcone derivative 4'-acetoamido-4-hydroxychalcone (ARC) as a potential therapeutic agent for the treatment of glioma. Treatment with ARC reduced glioma cell invasion, migration, and colony formation in a concentration-dependent manner In addition, AHC inhibited vascular endothelial growth factor-induced migration, invasion, and tube formation in HUVECs To determine the mechanism underlying the inhibitory effect of AHC on glioma cell invasion and migration, we investigated the effect of AHC on the gene expression change and found that AHC affects actin dynamics in U87MG glioma cells In actin cytoskeleton regulating system. ARC increased tropomyosin expression and stress fiber formation, probably through activation of PKA. Suppression of tropomyosin expression by siRNA or treatment with the PKA inhibitor H89 reduced the inhibitory effects of AHC on glioma cell invasion and migration In vivo experiments also showed that ARC inhibited tumor growth in a xenograft mouse tumor model Together, these data suggest that the synthetic chalcone derivative ARC has potent anti-cancer activity through inhibition of glioma proliferation, invasion, and angiogenesis and is therefore a potential chemotherapeutic candidate for the treatment of glioma Crown Copyright (C) 2010 Published by Elsevier Inc All rights reserved