DPMA, a deoxypodophyllotoxin derivative, induces apoptosis and anti-angiogenesis in non-small cell lung cancer A549 cells
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- 作者：Chun-Yan Sang ; Xiao-Hui Xu ; Wen-Wen Qin ; Jian-Fei Liu ; Lin Hui ; Shi-Wu Chen
- 关键词：Podophyllotoxin ; Deoxypodophyllotoxin ; Apoptosis ; Angiogenesis
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：15 December, 2013
- 年：2013
- 卷：23
- 期：24
- 页码：6650-6655
- 全文大小：1904 K
文摘
We found that the deoxypodophyllotoxin derivative, 2,6-dimethoxy-4-(6-oxo-(5R,5aR,6,8,8aR,9-hexahydrofuro[3鈥?4鈥?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.