Cordycepin induces apoptosis by enhancing JNK and p38 kinase activity and increasing the protein expression of Bcl-2 pro-apoptotic molecules

Objective:To explore the molecular mechanism by which cordycepin inhibits cell proliferation and induces apoptosis of human colorectal cancer cells.Methods:Cell counting and MTS(3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium,inner salt) method were used to monitor the effects of cordycepin on cell proliferation.Flow cytometry(FCM) was used to analyze the effects of cordycepin on the cell cycle progress.Annexin V-fluorescein isothiocyanate(FITC) analysis was used to detect apoptosis at a very early stage.Caspase-Glo was used to determine caspase activity and Western blot was used to measure protein expression levels of c-Jun N-terminal kinase(JNK),p38,and Bcl-2 pro-apoptosis family.Results:The numbers of viable SW480 and SW620 cells and the proliferation of these cells were significantly reduced with increases in cordycepin concentration(P<0.01).The cell cycle progression of SW480 and SW620 was arrested at the G0/G1 phase by the addition of cordycepin,and apoptosis rates of cordycepin treatments were increased compared with the control group.Cordycepin-treated cells showed phosphatidylserine valgus,suggesting the existence of early apoptosis.Caspase-3/7 and-9 activity significantly increased and the protein expression levels of JNK,p38,and Bax,Bid,Bim,and Puma from Bcl-2 pro-apoptosis molecules also increased after the treatment with cordycepin.Conclusions:Cordycepin can inhibit SW480 and SW620 cell proliferation and induce apoptosis.Apoptosis might be induced by enhancing JNK and p38 kinase activity and increasing the protein expression of Bcl-2 pro-apoptotic molecules.