The apoptotic effects of toosendanin are partially mediated by activation of deoxycytidine kinase in HL-60 cells

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 affi...

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Bibliographic Details
Published in:PloS one 2012-12, Vol.7 (12), p.e52536
Main Authors: Ju, Jianming, Qi, Zhichao, Cai, Xueting, Cao, Peng, Huang, Yan, Wang, Shuzhen, Liu, Nan, Chen, Yijun
Format: Article
Language:English
Subjects:
Activation
Affinity chromatography
Amino Acid Sequence
Analysis
Antineoplastic Agents - metabolism
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
Biology
Cancer
Catalytic Domain
Chemistry
Chinese medicine
Chromatography
Cytotoxicity
Deoxycytidine kinase
Deoxycytidine Kinase - chemistry
Deoxycytidine Kinase - genetics
Deoxycytidine Kinase - metabolism
Deoxyribonucleic acid
DNA
Drugs, Chinese Herbal - metabolism
Drugs, Chinese Herbal - pharmacology
Enzyme Activation - drug effects
Herbal medicine
HL-60 Cells
Humans
Insecticides
Kinases
Laboratories
Lymphocytes
Molecular Docking Simulation
Molecular Sequence Data
Mutagenesis
Mutation
Natural products
Pharmaceuticals
Phosphorylation
Protein binding
Proteins
Tumor cell lines
Tumor cells
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0052536