DPMA, a deoxypodophyllotoxin derivative, induces apoptosis and anti-angiogenesis in non-small cell lung cancer A549 cells

We found that the deoxypodophyllotoxin derivative, 2,6-dimethoxy-4-(6-oxo-(5R, 5aR, 6,8,8aR, 9-hexahydrofuro[ 30,40: 6,7] naphtho[2,3-d][1,3] dioxol-5-yl) phenyl ((R)-1-amino-4-(methylthio)-1-oxobutan-2-yl) carbamate (DPMA), exhibited superior cytotoxicity compared with etoposide. In this study, we investigated the mechanism of action of DPMA. DPMA exhibited anti-proliferative activity and induced apoptosis in A549 cells in a dose-and time-dependant manner. DPMA inhibited microtubule formation and induced expression of Bax, cleaved caspase-3, p53 and ROS, and inhibited Bcl-2 expression. DPMA also affected cyclinB1, cdc2 and p-cdc2 expression, inducing cell cycle arrest. DPMA also inhibited tube formation of VEGF-induced human umbilical vein endothelial cells. These studies demonstrate that DPMA inhibits p53/cdc2/Bax signaling, thereby inhibiting cell growth/angiogenesis and inducing apoptosis. (C) 2013 Elsevier Ltd. All rights reserved.