title: The apoptotic effects of toosendanin are partially mediated by activation of deoxycytidine kinase in HL-60 cells.
abstract: Triterpenoid toosendanin (TSN) exhibits potent cytotoxic activity through inducing apoptosis in a variety of cancer cell lines. However, the target and mechanism of the apoptotic effects by TSN remain unknown. In this study, we captured a specific binding protein of TSN in HL-60 cells by serial affinity chromatography and further identified it as deoxycytidine kinase (dCK). Combination of direct activation of dCK and inhibition of TSN-induced apoptosis by a dCK inhibitor confirmed that dCK is a target for TSN partially responsible for the apoptosis in HL-60 cells. Moreover, the activation of dCK by TSN was a result of conformational change, rather than auto-phosphorylation. Our results further imply that, in addition to the dATP increase by dCK activation in tumor cells, dCK may also involve in the apoptotic regulation.
authors.affiliation: State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Ju
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Qi
authors.forename: Xueting
authors.initials: X
authors.lastname: Cai
authors.forename: Peng
authors.initials: P
authors.lastname: Cao
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Wang
authors.forename: Nan
authors.initials: N
authors.lastname: Liu
authors.forename: Yijun
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020134:Catalytic Domain; D003842:Deoxycytidine Kinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000378:metabolism / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D014315:Triterpenes
chemical_list: D000970:Antineoplastic Agents; D003842:Deoxycytidine Kinase; D004365:Drugs, Chinese Herbal; C036454:toosendanin; D014315:Triterpenes