Acetylcholinesterase expression mediated by c-Jun-NH2-terminal kinase pathway during anticancer drug-induced apoptosis

Oncogene. 2006 Nov 9;25(53):7070-7. doi: 10.1038/sj.onc.1209686. Epub 2006 May 22.


It has been shown that acetylcholinesterase (AChE) expression was induced during apoptosis and the anti-sense oligonucleotides and siRNA of AChE may prevent apoptosis in various cell types. However, the mechanisms underlying AChE upregulation remain elusive. We demonstrated here that c-Jun NH2-terminal kinase (JNK) could mediate AChE expression. In this study, both etoposide and excisanin A, two anticancer agents, induced apoptosis in colon cancer cell line SW620 as determined by Annexin V staining, the cleavage of caspase-3 and the proteolytic degradation of poly (ADP-ribose) polymerase (PARP). The results showed that both the agents upregulated AChE in SW620 cells. In the meantime, JNK was also activated and the expression and phosphorylation of c-Jun increased in SW620 cells exposed to the two agents. The induced AChE mRNA and protein expression could be blocked by SP600125, a specific inhibitor of SAPK/JNK, and small interfering RNA directed against JNK1/2. Transfection with adenovirus-mediated dominant negative c-Jun also blocked the upregulation of AChE expression. Together, these results suggest that AChE expression may be mediated by the activation of JNK pathway during apoptosis through a c-Jun-dependent mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / genetics
  • Acetylcholinesterase / metabolism*
  • Adenoviridae / genetics
  • Anthracenes / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cytoprotection / drug effects
  • Diterpenes / pharmacology*
  • Enzyme Activation / drug effects
  • Etoposide / pharmacology*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • JNK Mitogen-Activated Protein Kinases / genetics
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Poly(ADP-ribose) Polymerases / metabolism
  • RNA, Small Interfering / genetics
  • Signal Transduction / drug effects*
  • Up-Regulation / drug effects


  • Anthracenes
  • Antineoplastic Agents
  • Diterpenes
  • RNA, Small Interfering
  • pyrazolanthrone
  • Etoposide
  • excisanin A
  • Poly(ADP-ribose) Polymerases
  • JNK Mitogen-Activated Protein Kinases
  • Acetylcholinesterase
  • Caspase 3