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http://dx.doi.org/10.5352/JLS.2014.24.1.92

Induction of Apoptosis and G2/M Cell Cycle Arrest by Cordycepin in Human Prostate Carcinoma LNCap Cells  

Lee, Hye Hyeon (Department of Biotechnology, College of Natural Resources and Life Science, Dong-A University)
Hwang, Won Deok (Department of Internal Medicine, Dongeui University College of Oriental Medicine)
Jeong, Jin-Woo (Center for Core Research Facilities, Daegu-Gyeongbuk Institute of Science & Technology)
Park, Cheol (Department of Molecular Biology, College of Natural Sciences, Dongeui University)
Han, Min Ho (Department of Biochemistry, Dongeui University College of Oriental Medicine)
Hong, Su Hyun (Department of Biochemistry, Dongeui University College of Oriental Medicine)
Jeong, Yong Kee (Department of Biotechnology, College of Natural Resources and Life Science, Dong-A University)
Choi, Yung Hyun (Department of Biochemistry, Dongeui University College of Oriental Medicine)
Publication Information
Journal of Life Science / v.24, no.1, 2014 , pp. 92-97 More about this Journal
Abstract
Cordycepin, an active component originally isolated from the traditional medicine Cordyceps militaris, is a derivative of the nucleoside adenosine, which has been shown to possess a number of pharmacological properties, including antioxidant and anti-inflammatory activities, immunological stimulation, and antitumor effects. This study was conducted on cultured human prostate carcinoma LNCap cells to elucidate the possible mechanisms by which cordycepin exerts its anticancer activity, which, until now, has remained poorly understood. Cordycepin treatment of LNCap cells resulted in dose-dependent inhibition of cell growth and the induction of apoptotic cell death as detected by an MTT assay, cleavage of poly ADP-ribose polymerase, and annexin V-FITC staining. Flow cytometric analysis revealed that cordycepin resulted in G2/M arrest in cell cycle progression and downregulation of cyclin B1 and cyclin A expression in a concentration-dependent manner. Moreover, the incubation of cells with cordycepin caused a striking induction in the expression of the cyclin-dependent kinase (CDK) inhibitor p21Waf1/Cip1 without affecting the expression of the tumor suppressor p53. It also resulted in a significant increase in the binding of CDK2 and CDC2 to p21. These findings suggest that cordycepin-induced G2/M arrest and apoptosis in human prostate carcinoma cells is mediated through p53-independent upregulation of the CDK inhibitor p21.
Keywords
Apoptosis; cordycepin; G2/M arrest; p21; prostate carcinoma LNCap cells;
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