title: ZC88, a novel 4-amino piperidine analog, inhibits the growth of neuroblastoma cells through blocking hERG potassium channel.
abstract: Many studies have provided convincing evidence for hERG as an important diagnostic and prognostic factor in human cancers, as well as a useful target for antineoplastic therapy. Our previous study also revealed that knockdown of herg gene expression by shRNA interference inhibited the growth of neuroblastoma cells in vitro and in vivo. In the experiment, a novel 4-amino piperidine analog, ZC88, was examined for its effect on hERG potassium channels and its antitumor potency was observed in vitro and in vivo. The results showed that ZC88 could block hERG1 and hERG1b channels expressed in Xenopus oocytes in a concentration-dependent manner. ZC88 displayed significant antiproliferative activity in several tumor cell lines and the tumor cells with higher expression of hERG presented higher sensitivity to ZC88. The mitotic progression of tumor cells was markedly suppressed in the presence of ZC88 through arresting cells in G₀/G₁ phase. ZC88 significantly inhibited the tumor growth in nude mice at a dosage with slight influence on the cardiac QT interval. The antitumor effect of ZC88 was correlated at least partly with its blockage of hERG channels, which implicated a positive role of hERG potassium channel in tumor cell proliferation.
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wei
authors.forename: Hongliang
authors.initials: H
authors.lastname: Sun
authors.forename: Haitao
authors.initials: H
authors.lastname: Yan
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Shuzhuo
authors.initials: S
authors.lastname: Zhang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.forename: Nan
authors.initials: N
authors.lastname: Hua
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Ma
authors.forename: Jianquan
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010880:Piperidines / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays; D014982:Xenopus laevis
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; C531033:N-(1-(2,3-dimethoxyphenyl)-4-methyl-3-penten-1-yl)-1-(5-bromofurfuryl)-1-piperidyl-4-amine; D010880:Piperidines; D026902:Potassium Channel Blockers
keywords: 4-aminopiperidine; SH-SY5Y; cancer; cell cycle; hERG; neuroblastoma; potassium channel
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