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: Jianming Ju, Zhichao Qi, Xueting Cai, Peng Cao, Yan Huang, Shuzhen Wang, Nan Liu, Yijun Chen
• Journal: PloS one (PLoS One) Vol. 7 Issue 12 Pg. e52536 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 23300702 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Drugs, Chinese Herbal
• toosendanin
• Deoxycytidine Kinase

Topics

• Amino Acid Sequence
• Antineoplastic Agents (metabolism, pharmacology)
• Apoptosis (drug effects)
• Catalytic Domain
• Deoxycytidine Kinase (chemistry, genetics, metabolism)
• Drugs, Chinese Herbal (metabolism, pharmacology)
• Enzyme Activation (drug effects)
• HL-60 Cells
• Humans
• Molecular Docking Simulation
• Molecular Sequence Data
• Mutagenesis
• Mutation