Anti-Oncogenic gem-Dihydroperoxides Induce Apoptosis in Cancer Cells by Trapping Reactive Oxygen Species

International Journal of Molecular Sciences

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

【 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】

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