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

Arch Biochem Biophys. 2009 Oct 15;490(2):103-9. doi: 10.1016/ Epub 2009 Sep 5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthracenes / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Cell Cycle / drug effects*
  • Cell Cycle / 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
  • JNK Mitogen-Activated Protein Kinases / genetics
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • MAP Kinase Signaling System / drug effects
  • Protein Kinase Inhibitors / pharmacology
  • RNA, Small Interfering / genetics
  • Up-Regulation / drug effects
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology


  • 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