Cordycepin Downregulates Cdk-2 to Interfere with Cell Cycle and Increases Apoptosis by Generating ROS in Cervical Cancer Cells: in vitro and in silico Study
[ Vol. 18 , Issue. ]
Mousumi Tania, Jakaria Shawon, Kazi Saif, Rudolf Kiefer, Mahdi Safaei Khorram, Mohammad A Halim and Md. Asaduzzaman Khan*Pages 1-8 (8)
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 indicated 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 that 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.
Cordycepin, Cervical cancer, Apoptosis, Reactive oxygen species, Cell cycle, Cdk2
Division of Molecular Cancer Biology, The Red-Green Research Center, Dhaka, Division of Molecular Cancer Biology, The Red-Green Research Center, Dhaka, Division of Molecular Cancer Biology, The Red-Green Research Center, Dhaka, Conducting polymers in composites and applications Research Group, Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou, Division of Molecular Cancer Biology, The Red-Green Research Center, Dhaka, Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000
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