Cordycepin is a small molecule from medicinal mushroom Cordyceps, which has been reported for anticancer properties. In this study, we investigated cordycepin effect on cervical cancer cells in vitro. Results indicate that treatment of cordycepin controlled SiHa and Hela cervical cancer cell growth, increased the rate of their apoptosis, and interfered with cell cycle, specifically elongated S-phase. By using qPCR, we investigated the expression of anti-apoptotic and pro-apoptotic proteins as well as cell cycle protein's expression in mRNA levels, and found there was a downregulation of cell cycle proteins CDK-2, CYCLIN-A2 and CYCLIN-E1 by cordycepin treatment but no significant change in pro-apoptotic or anti-apoptotic proteins. The intracellular reactive oxygen species (ROS) level in cordycepin treated cells was increased significantly, implying that apoptosis might be induced by ROS. Western blot analysis confirmed significant decrease of Cdk-2 and mild decrease of Cyclin-E1 and Cyclin-A2 by cordycepin, which might be responsible for regulating cell cycle. Molecular docking simulation indicated high binding affinity of cordycepin against Cdk-2. Molecular dynamics simulation further confirmed that the docked pose of cordycepin-Cdk2 complex remained within the binding pocket for 10ns. Thus, our study suggests that cordycepin is effective against cervical cancer cells, and regulating cell cycle via cell cycle proteins, especially downregulating Cdk-2, and inducing apoptosis by generating ROS are among the mechanisms of anticancer activities of cordycepin.
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