Dioscin induces cancer cell apoptosis through elevated oxidative stress mediated by downregulation of peroxiredoxins.
Dioscin has been shown to promote anticancer activity against several forms of cancers. However, its detailed molecular mechanisms have not been clearly clarified.In this study, we demonstrate that dioscin induces apoptosis in cancer cells through the induction of oxidative stress. Treatment with cancer cells in vitro with dioscin resulted in rapid generation of reactive oxygen species (ROS) and the induction of mitochondrial pathway apoptosis in human esophageal cancer cell line Kyse510. Inhibition of oxidative stress by the antioxidant N-acetylcysteine blocked the induction of apoptosis by dioscin, indicating that ROS generation is the primary mechanism responsible for the proapoptotic activity of dioscin. Proteomic analysis and protein gel blotting further revealed peroxiredoxins 1 and 6 (PRDX 1 and 6), which are implicated in ROS metabolism and apoptosis, were associated with the anticancer effects of dioscin. Meanwhile, overexpression of PRDX 1 and 6 significantly blocked the elevated ROS and apoptosis induced by dioscin. In conclusion, we suggest that PRDX1 and PRDX6 are key targets in the process of dioscin-induced apoptosis that involves intracellular elevated ROS.
School of Chinese Medicine, The University of Hong Kong, Hong Kong, China.
Zhiyu
Z
Wang
Yue
Y
Cheng
Neng
N
Wang
Dong Mei
DM
Wang
Ying Wei
YW
Li
Feng
F
Han
Jian Gang
JG
Shen
De Po
DP
Yang
Xin Yuan
XY
Guan
Jian-Ping
JP
Chen
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D018384:Oxidative Stress; D054465:Peroxiredoxin VI / Q000235:genetics* / Q000378:metabolism; D054464:Peroxiredoxins / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; C019357:dioscin; C515940:PRDX1 protein, human; C515977:PRDX6 protein, human; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; D020169:Caspases; D004144:Diosgenin