Study On The Anti-tumor Activities And Mechanisms Of A Cordyceps Sinensis Fungus

Cordyceps sinensis (Cs) or Dongchongxiacao in Chinese is a special type of mushroom, which is formed on an insect larva infected by the Cs fungus. It is a rare and precious medicinal mushroom having great medicinal value. Considerable research effort has been made to evaluate the anti-tumor effects of Cordyceps species. However, most of these studies were focused on the water or ethanol extract, and the mechanisms of the anti-tumor activity are still not well understood.In this study, an anamorph of Cs fungus was isolated, designated as HK-1 and was cultivated in liquid. The anti-tumor effects of the cultivated fungus mycelium were investigated. The results showed that Cs fungus HK-1 EtOAc extract had significant anti-tumor effect.Now, many cancer drugs have been shown to induce the apoptosis of cancer cells. Therefore, apoptosis induction may be one possible mechanism responsible for their anti-tumor function. After the anti-tumor activity of Cs fungus HK-1 EtOAc extract was confirmed, we investigated its mechanism further. The results indicate that Cs fungus HK-1 EtOAc extract can induce HL-60 apoptosis, and caspase-3 participates in the process.In the process of mammalian cell apoptosis, mitochondrion was considered being the center of apoptotic regulation and cytochrome c was key molecular. Previous studies have suggested that some members of Bcl-2 family were important in the mitochondria pathway of apoptosis. Therefore, a series of experiments was done for illustrating the signal pathway of HL-60 cell apoptosis induced by Cs fungus HK-1 EtOAc extract and the effects of Bcl-2 family members Bcl-2 and Bax. The results suggest that the mitochondrion-related signal pathway started the apoptotic cell death induced by Cs fungus HK-1 EtOAc extract.In order to more fully understand the anti-tumor effects of Cs fungus HK-1 EtOAc extract, its effect on the cell cycle was tested by flow cytometer. Theresults showed that cells were arrested at G₂/M phase after treated with Cs fungus HK-1 EtOAc extract and the content of G₂/M related protein p34^cdc2 decreased.This project studied extensively the anti-tumor activity of Cs fungus HK-1 and found that the EtOAc extract had potent anti-tumor activity in vitro and in vivo. The activity could be partially attributed to the induction of apoptotic cell death through mitochondrion-related signal pathway and induction of cell cycle G₂/M arrest. The results offered not only evidence for exploiting Cordyceps sinensis and studying anti-tumor drugs, but also clue to illustrating apoptosis process.