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

Abstract

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.

• Authors: R Deng, W Li, Z Guan, J-M Zhou, Y Wang, Y-P Mei, M-T Li, G-K Feng, W Huang, Z-C Liu, Y Han, Y-X Zeng, X-F Zhu
• Journal: Oncogene (Oncogene) Vol. 25 Issue 53 Pg. 7070-7 (Nov 09 2006) ISSN: 0950-9232 [Print] England
• PMID: 16715131 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Acetylcholinesterase (genetics, 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, metabolism)
• Poly(ADP-ribose) Polymerases (metabolism)
• RNA, Small Interfering (genetics)
• Signal Transduction (drug effects)
• Up-Regulation (drug effects)