• Huei-Mei Chen, Fang-Rong Chang, Ya-Ching Hsieh, Yu-Jen Cheng, Kun-Chou Hsieh, Lih-Min Tsai, An-Shen Lin, Yang-Chang Wu, and Shyng-Shiou Yuan.
• Department of Medical Research, E-DA Hospital, Kaohsiung 824, Taiwan, Republic of China.
• Free Radic. Biol. Med. 2011 May 1; 50 (9): 1151-62.

AbstractThe protoapigenone analogue WYC02-9, a novel synthetic flavonoid, has been shown to act against a variety of experimental tumors. However, its effects on prostate cancer and its mechanism of action are unknown. Thus, WYC02-9 was investigated for its cytotoxicity against DU145 prostate cancer cells, as was the underlying mechanisms by which WYC02-9 might induce DNA damage and apoptotic cell death through reactive oxygen species (ROS). WYC02-9 inhibited the cell growth of three prostate cancer cell lines, especially DU145 cells. In DU145 cells, WYC02-9 increased the generation of intracellular ROS, followed by induction of DNA damage and activation of the ATM-p53-H2A.X pathway and checkpoint-related signals Chk1/Chk2, which led to increased numbers of cells in the S and G2/M phases of the cell cycle. Furthermore, WYC02-9 induced apoptotic cell death through mitochondrial membrane potential decrease and activation of caspase-9, caspase-3, and PARP. The above effects were all prevented by the ROS scavenger N-acetylcysteine. Administration of WYC02-9 in a nude mouse DU145 xenograft model further identified the anti-cancer activity of WYC02-9. These findings therefore suggest that WYC02-9-induced DNA damage and mitochondria-dependent cell apoptosis in DU145 cells are mediated via ROS generation.Copyright © 2011 Elsevier Inc. All rights reserved.

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