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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. 19 , Issue. 2 ]

Author(s):

Mousumi Tania, Jakaria Shawon, Kazi Saif, Rudolf Kiefer, Mahdi Safaei Khorram, Mohammad A. Halim* and Md. Asaduzzaman Khan*Pages 152-159 (8)

Abstract:


Background: Cordycepin is a small molecule from medicinal mushroom Cordyceps, which has been reported for anticancer properties.

Objective: In this study, we have focused on the investigation of cordycepin effect on cervical cancer cells with further clarification of possible molecular mechanism.

Method: We have used cell viability and cell counting assay for cytotoxic effect of cordycepin, flow cytometric assay of apoptosis and cell cycle, and quantitative PCR (qPCR) and Western blotting for the determination of target gene expression. Molecular docking and Molecular dynamics simulation were used for in silico analysis of cordycepin affinity to target protein(s).

Results: 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. qPCR results indicated that there was a downregulation of cell cycle proteins CDK-2, CYCLIN-A2 and CYCLIN-E1 in mRNA level by cordycepin treatment but no significant change was observed in pro-apoptotic or antiapoptotic 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 indicated high binding affinity of cordycepin against Cdk-2. Molecular dynamics simulation further confirmed that the docked pose of cordycepin-Cdk-2 complex remained within the binding pocket for 10 ns.

Conclusion: 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.

Keywords:

Cordycepin, cervical cancer, apoptosis, reactive oxygen species, cell cycle, Cdk-2.0007U

Affiliation:

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, Division of Molecular Cancer Biology, The Red-Green Research Center, Dhaka

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