Background: Cordycepin possesses anti-inflammatory, anti-metastatic and anti-tumor properties.
Objective: The present study investigates the anti-hepatocellular carcinoma activities of cordycepin in in vitro and in
Method: Cell viability, apoptosis rate, intracellular reactive oxygen species (ROS) level and mitochondrial membrane
potential (MMP) were determined by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide bromide assay,
annexin V/propidium iodide double staining, 2',7'-dichlorfluorescein-diacetate and 5,5’,6,6’-tetrachloro-1,1’,3,3’
tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining respectively. The expressions of pro-apoptosis and antiapoptosis
proteins were detected by western blot. A PLC/PRL/5-xenografted nude mouse model was applied to further
confirm the anti-tumor activities of cordycepin.
Results: Cordycepin suppressed cell viability, enhanced apoptotic rate, inhibited cell proliferation and increased
cleaved poly (ADP-ribose) polymerase (PARP) level. Apoptotic alteration on mitochondria and abnormal changes on
b-cell lymphoma 2 (Bcl-2) and b-cell lymphoma-extra large (Bcl-xL) levels were observed in cordycepin-treated cells.
Furthermore, cordycepin suppressed the activation of extracellular signaling-regulated kinase (ERKs) and mammalian
target of rapamycin (mTOR) in both PLC/PRF/5 and HepG2 cells. Finally, PLC/PRL/5-xengrafted BALB/c athymic
nude mice were performed to confirm cordycepin’s anti-tumor action.
Conclusion: Our finding suggests that the anti-hepatocellular carcinoma properties of cordycepin are related to its
modulation of multiple anti-apoptotic and pro-apoptotic pathways. Our study provides an experimental evidence for
cordycepin as a rational agent for hepatocellular carcinoma treatment.