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Oncotarget. 2016 Sep 13;7(37):60270-60289. doi: 10.18632/oncotarget.11201.

Systematic revelation of the protective effect and mechanism of Cordycep sinensis on diethylnitrosamine-induced rat hepatocellular carcinoma with proteomics.

Wang PW1, Hung YC1,2, Li WT3, Yeh CT4, Pan TL1,4,5,6.

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School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan.
Department of Chinese Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung City, Taiwan.
National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan.
Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.


Cordyceps sinensis (C. sinensis) has been reported to treat liver diseases. Here, we investigated the inhibitory effect of C. sinensis on hepatocarcinoma in a diethylnitrosamine (DEN)-induced rat model with functional proteome tools.In the DEN-exposed group, levels of serum alanine aminotransferase and aspartate aminotransferase were increased while C. sinensis application remarkably inhibited the activities of these enzymes. Histopathological analysis also indicated that C. sinensis could substantially restore hypertrophic hepatocytes caused by DEN, suggesting that C. sinensis is effective in preventing DEN-induced hepatocarcinogenesis.We therefore comprehensively delineated the global protein alterations using a proteome platform. The most meaningful changes were found among proteins involved in oxidative stress and detoxification. Meanwhile, C. sinensis application could attenuate the carbonylation level of several enzymes as well as chaperone proteins. Network analysis implied that C. sinensis could obviously alleviate hepatocarcinoma via modulating redox imbalance, protein ubiquitination and tumor growth-associated transcription factors.Our findings provide new insight into the potential effects of C. sinensis in preventing carcinogenesis and might help in developing novel therapeutic strategies against chemical-induced hepatocarcinoma.


Cordycep sinensis; diethylnitrosamine; hepatocellular carcinoma; proteomics

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