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Abstract: 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.

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