Cordycepin causes p21WAF1-mediated G2/M cell-cycle arrest by regulating c-Jun N-terminal kinase activation in human bladder cancer cells.

Abstract

Cordycepin (3'-deoxyadenosine), a bioactive compound of Cordyceps militaris, has many pharmacological activities. The present study reveals novel molecular mechanisms for the anti-tumor effects of cordycepin in two different bladder cancer cell lines, 5637 and T-24 cells. Cordycepin treatment, at a dose of 200 microM (IC(50)) during cell-cycle progression resulted in significant and dose-dependent growth inhibition, which was largely due to G2/M-phase arrest, and resulted in an up-regulation of p21WAF1 expression, independent of the p53 pathway. Moreover, treatment with cordycepin-induced phosphorylation of JNK (c-Jun N-terminal kinases). Blockade of JNK function using SP6001259 (JNK-specific inhibitor) and small interfering RNA (si-JNK1) rescued cordycepin-dependent p21WAF1 expression, inhibited cell growth, and decreased cell cycle proteins. These results suggest that cordycepin could be an effective treatment for bladder cancer.

• Authors: Se-Jung Lee, Si-Kwan Kim, Won-Seok Choi, Wun-Jae Kim, Sung-Kwon Moon
• Journal: Archives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 490 Issue 2 Pg. 103-9 (Oct 15 2009) ISSN: 1096-0384 [Electronic] United States
• PMID: 19733546 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthracenes
• Antineoplastic Agents
• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• Deoxyadenosines
• Protein Kinase Inhibitors
• RNA, Small Interfering
• pyrazolanthrone
• JNK Mitogen-Activated Protein Kinases
• cordycepin

Topics

• Anthracenes (pharmacology)
• Antineoplastic Agents (pharmacology)
• Cell Cycle (drug effects, physiology)
• Cell Division (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cyclin-Dependent Kinase Inhibitor p21 (metabolism)
• Deoxyadenosines (pharmacology)
• Enzyme Activation (drug effects)
• G2 Phase (drug effects)
• Humans
• JNK Mitogen-Activated Protein Kinases (antagonists & inhibitors, genetics, metabolism)
• MAP Kinase Signaling System (drug effects)
• Protein Kinase Inhibitors (pharmacology)
• RNA, Small Interfering (genetics)
• Up-Regulation (drug effects)
• Urinary Bladder Neoplasms (drug therapy, metabolism, pathology)