期刊论文详细信息
International Journal of Molecular Sciences
Anti-Oncogenic gem-Dihydroperoxides Induce Apoptosis in Cancer Cells by Trapping Reactive Oxygen Species
Yuki Kuranaga3  Nami Yamada3  Maiko Kashiwaya2  Moeko Nakamura2  Lei Cui2  Minami Kumazaki3  Haruka Shinohara3  Nobuhiko Sugito3  Kohei Taniguchi3  Yuko Ito1  Tatsushi Nakayama2  Bunji Uno2  Akichika Itoh2  Yukihiro Akao3 
[1] Department of Anatomy and Cell Biology, Division of Life Sciences, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan;Department of Pharmacy, Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu 501-1196, Japan;United Graduate School of Drug Discovery and Information Science, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan;
关键词: apoptosis;    ROS;    dihydroperoxide;    JNK/MAPK;    cancer cell;   
DOI  :  10.3390/ijms17010071
来源: mdpi
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【 摘 要 】

Organic gem-dihydroperoxides (DHPs) and their derived peroxides have attracted a great deal of attention as potential anti-cancer agents. However, the precise mechanism of their inhibitory effect on tumors is unknown. To determine the mechanism of the inhibitory effects of DHPs, we examined the effects of DHPs on leukemia K562 cells. As a result, certain DHPs used in this study exhibited growth-inhibitory activity according to a clear structure-activity relationship. The most potent DHP, 12AC3O, induced apoptosis in K562 cells, but not in peripheral blood monocytes (PBMCs) or fibroblast cells. 12AC3O induced apoptosis through the intrinsic mitochondrial pathway and thereafter through the extrinsic pathway. The activity of the former pathway was partly attenuated by a JNK inhibitor. Interestingly, 12AC3O induced apoptosis by trapping a large amount of ROS, leading to an extremely lower intracellular ROS level compared with that in the cells in the steady-state condition. These results suggest that an appropriate level of intracellular ROS was necessary for the maintenance of cancer cell growth. DHPs may have a potential to be a novel anti-cancer agent with minimum adverse effects on normal cells.

【 授权许可】

CC BY   
© 2016 by the authors; licensee MDPI, Basel, Switzerland.

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