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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.

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Acknowledgements

We thank Professor You-Heng Gao from Guangzhou University of Traditional Chinese Medicine School of Pharmaceutical Science for providing excisanin A. This work was supported by the National Natural Science Foundation of China (No. 30472037, 30572363), 973 program (2004CB518801) and the Research Grants Committee of Hong Kong (HKUST 6120/02M, 6133/03M; AoE/B15/01).

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Correspondence to Y Han or X-F Zhu.

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Deng, R., Li, W., Guan, Z. et al. Acetylcholinesterase expression mediated by c-Jun-NH2-terminal kinase pathway during anticancer drug-induced apoptosis. Oncogene 25, 7070–7077 (2006). https://doi.org/10.1038/sj.onc.1209686

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