c-Jun N-terminal kinase 1 is required for cordycepin-mediated induction of G2/M cell-cycle arrest via p21WAF1 expression in human colon cancer cells

Food Chem Toxicol. 2010 Jan;48(1):277-83. doi: 10.1016/j.fct.2009.09.042. Epub 2009 Oct 13.


Cordycepin (3'-deoxyadenosine) has many anti-cancer properties. However, neither its molecular mechanism nor its molecular targets are well understood. In the present study, we investigated novel molecular mechanisms for the anti-tumor effects of cordycepin in human colon cancer HCT116 cells. After treatment of cells with cordycepin, dose-dependent cell growth inhibition was observed at an IC(50) value of 200muM. Cordycepin treatment resulted in G2/M-phase cell-cycle arrest, which was associated with increased p21WAF1 levels and reduced amounts of cyclin B1, Cdc2, and Cdc25c in a p53-independent pathway. Moreover, cordycepin treatment induced activation of JNK (c-Jun N-terminal kinases). Pretreatment with SP600125, a JNK-specific inhibitor, abrogated cordycepin-mediated p21WAF1 expression, cell growth inhibition, and reduced cell-cycle proteins. Furthermore, JNK1 inhibition by small interfering RNA (siRNA) produced similar results: suppression of cordycepin-induced p21WAF1 expression, decreased cell growth, and reduced cell-cycle proteins. Together, these results suggest a critical role for JNK1 activation in cordycepin-induced inhibition of cell growth and G2/M-phase arrest in human colon cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthracenes / pharmacology
  • Apoptosis / drug effects
  • Blotting, Western
  • Cell Cycle / drug effects
  • Cell Division / drug effects*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Colonic Neoplasms / enzymology*
  • Colonic Neoplasms / pathology*
  • Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis*
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Deoxyadenosines / pharmacology*
  • Enzyme Inhibitors / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Signal-Regulated MAP Kinases / biosynthesis
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • G2 Phase / drug effects*
  • Humans
  • Immunoprecipitation
  • Mitogen-Activated Protein Kinase 8 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 8 / metabolism*
  • Mitogen-Activated Protein Kinase 9 / metabolism
  • RNA, Small Interfering / genetics
  • p38 Mitogen-Activated Protein Kinases / biosynthesis
  • p38 Mitogen-Activated Protein Kinases / genetics


  • Anthracenes
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Deoxyadenosines
  • Enzyme Inhibitors
  • RNA, Small Interfering
  • pyrazolanthrone
  • Mitogen-Activated Protein Kinase 9
  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinase 8
  • p38 Mitogen-Activated Protein Kinases
  • cordycepin