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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.

SUBMITTER: Ju J

PROVIDER: S-EPMC3531419 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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

Ju Jianming J Qi Zhichao Z Cai Xueting X Cao Peng P Huang Yan Y Wang Shuzhen S Liu Nan N Chen Yijun Y

PloS one 20121227 12

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 ...[more]

PMID: 23300702

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