title: 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.affiliation: State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: R
authors.initials: R
authors.lastname: Deng
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: Z
authors.initials: Z
authors.lastname: Guan
authors.forename: J-M
authors.initials: JM
authors.lastname: Zhou
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: Y-P
authors.initials: YP
authors.lastname: Mei
authors.forename: M-T
authors.initials: MT
authors.lastname: Li
authors.forename: G-K
authors.initials: GK
authors.lastname: Feng
authors.forename: W
authors.initials: W
authors.lastname: Huang
authors.forename: Z-C
authors.initials: ZC
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Han
authors.forename: Y-X
authors.initials: YX
authors.lastname: Zeng
authors.forename: X-F
authors.initials: XF
authors.lastname: Zhu
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism*; D000256:Adenoviridae / Q000235:genetics; D000873:Anthracenes / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D019610:Cytoprotection / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000873:Anthracenes; D000970:Antineoplastic Agents; D004224:Diterpenes; D034741:RNA, Small Interfering; C432165:pyrazolanthrone; D005047:Etoposide; C047381:excisanin A; D011065:Poly(ADP-ribose) Polymerases; D048031:JNK Mitogen-Activated Protein Kinases; D000110:Acetylcholinesterase; D053148:Caspase 3