Abstract
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.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors and the third leading cause of cancer death worldwide [1]
In the DEN-treated group at 17 weeks (17 W), the nodules were separated by thick fibrous bands with varying degrees of cellular differentiation and lymphocyte infiltration (Figure 3a) whereas C. sinensis administration obviously alleviated these pathological changes and showed normal liver www.impactjournals.com/oncotarget histology with well-developed and orderly arranged hepatocytes (Figure 3b)
A great number of conventional medicines have been applied to liver diseases, and some herbal remedies have been useful in the management of hepatic tumors [26, 27]
Summary
Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors and the third leading cause of cancer death worldwide [1]. In spite of current advances in the use of synthetic drugs, several shortcomings such as efficacy and side effects still remain [2]. There is an urgent need for alternative and effective agents for the management of hepatocellular carcinoma, with better efficacy and less detriment [3]. The major causes of HCC are known as hepatitis B or. Recent studies have indicated that formation of reactive oxygen species (ROS) within hepatocytes would eventually result in the cytotoxic effect [6]. ROS-caused oxidation of target proteins or enzymes would negatively influence their normal functions, which might lead to hepatocarcinogenesis [7]. Simultaneous treatment with antioxidants, especially at the early stages, might be a breakthrough in HCC interventions
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