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.

作者: Mousumi Tania , Jakaria Shawon , Kazi Saif , Rudolf Kiefer , Mahdi S Khorram

DOI: 10.2174/1568009618666180905095356

关键词:

摘要: 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 cervical cancer cells with further clarification possible molecular mechanism. Method We used cell viability and counting assay cytotoxic cordycepin, flow cytometric apoptosis cycle, quantitative PCR (qPCR) Western blotting determination target gene expression. Molecular docking dynamics simulation were in silico analysis affinity to protein(s). Results Treatment controlled SiHa HeLa growth, increased rate their apoptosis, interfered specifically elongated S-phase. qPCR results indicated that there was downregulation cycle proteins CDK-2, CYCLIN-A2 CYCLIN-E1 mRNA level by treatment but no significant change observed pro-apoptotic or antiapoptotic proteins. The intracellular reactive oxygen species (ROS) treated significantly, implying might be induced ROS. blot confirmed decrease Cdk-2 mild Cyclin-E1 Cyclin-A2 responsible regulating cycle. high binding against Cdk-2. docked pose cordycepin-Cdk-2 complex remained within pocket 10 ns. Conclusion Our study suggests effective cells, via proteins, especially downregulating Cdk-2, inducing generating ROS are among mechanisms activities cordycepin.

参考文章(42)
Yuanhong Liao, Jianya Ling, Guoying Zhang, Fengjun Liu, Shengce Tao, Zeguang Han, Saijuan Chen, Zhu Chen, Huangying Le, Cordycepin induces cell cycle arrest and apoptosis by inducing DNA damage and up-regulation of p53 in Leukemia cells Cell Cycle. ,vol. 14, pp. 761- 771 ,(2015) , 10.1080/15384101.2014.1000097
Satomi Kagota, Arisa Nishiuchi, Noriko Yoshikawa, Yoko Kimoto, Erika Kubo, Kazumasa Shinozuka, Yuta Takahashi, Ayuko Sato, Kazuki Nakamura, Mami Kakuda, Inhibitory effect of cordycepin on experimental hepatic metastasis of B16-F0 mouse melanoma cells. in Vivo. ,vol. 27, pp. 729- 732 ,(2013)
Md. Asaduzzaman Khan, Mousumi Tania, Chunli Wei, Zhiqiang Mei, Shelly Fu, Jingliang Cheng, Jianming Xu, Junjiang Fu, Thymoquinone inhibits cancer metastasis by downregulating TWIST1 expression to reduce epithelial to mesenchymal transition Oncotarget. ,vol. 6, pp. 19580- 19591 ,(2015) , 10.18632/ONCOTARGET.3973
Pu Zhang, Changjin Huang, Changliang Fu, Yang Tian, Yijuan Hu, Bochu Wang, Amy Strasner, Yang Song, Erqun Song, Cordycepin (3′-deoxyadenosine) suppressed HMGA2, Twist1 and ZEB1-dependent melanoma invasion and metastasis by targeting miR-33b Oncotarget. ,vol. 6, pp. 9834- 9853 ,(2015) , 10.18632/ONCOTARGET.3383
Md Asaduzzaman Khan, Han-chun Chen, Xin-xing Wan, Mousumi Tania, Ai-hua Xu, Fang-zhi Chen, Dian-zheng Zhang, None, Regulatory effects of resveratrol on antioxidant enzymes: A mechanism of growth inhibition and apoptosis induction in cancer cells Molecules and Cells. ,vol. 35, pp. 219- 225 ,(2013) , 10.1007/S10059-013-2259-Z
Caterina Bissantz, Bernd Kuhn, Martin Stahl, A Medicinal Chemist’s Guide to Molecular Interactions Journal of Medicinal Chemistry. ,vol. 53, pp. 5061- 5084 ,(2010) , 10.1021/JM100112J
Wei-Ciao Wu, Jenn-Ren Hsiao, Yu-Yan Lian, Chun-Yu Lin, Bu-Miin Huang, The apoptotic effect of cordycepin on human OEC-M1 oral cancer cell line. Cancer Chemotherapy and Pharmacology. ,vol. 60, pp. 103- 111 ,(2007) , 10.1007/S00280-006-0354-Y
Kazuki Nakamura, Kazumasa Shinozuka, Noriko Yoshikawa, Anticancer and antimetastatic effects of cordycepin, an active component of Cordyceps sinensis. Journal of Pharmacological Sciences. ,vol. 127, pp. 53- 56 ,(2015) , 10.1016/J.JPHS.2014.09.001
Florian Krieger, Beat Fierz, Oliver Bieri, Mario Drewello, Thomas Kiefhaber, Dynamics of unfolded polypeptide chains as model for the earliest steps in protein folding. Journal of Molecular Biology. ,vol. 332, pp. 265- 274 ,(2003) , 10.1016/S0022-2836(03)00892-1
Hardeep S. Tuli, Anil K. Sharma, Sardul S. Sandhu, Dharambir Kashyap, Cordycepin: a bioactive metabolite with therapeutic potential. Life Sciences. ,vol. 93, pp. 863- 869 ,(2013) , 10.1016/J.LFS.2013.09.030