1. ¹State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China
2. ²Department of Biochemistry, the Hong Kong University of Science and Technology, Kowloon, Hong Kong
3. ³Department of Pharmacology, Proteomics Lab, Sun Yat-sen University, Guangzhou, China

Correspondence: Dr X-F Zhu, State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, 651 DongFeng Road East, Guangzhou 510060, China. E-mail: xfzhu70@public.guangzhou.gd.cn; Y Han, Department of Biochemistry, Hong Kong University of Science and Technology, Kowloon, Hong Kong. E-mail: bcyfhan@ust.hk

Received 6 February 2006; Revised 6 April 2006; Accepted 8 April 2006; Published online 22 May 2006.

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.