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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]

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