Abrogation of G2/M arrest sensitizes curcumin-resistant hepatoma cells to apoptosis

被引:65
作者
Wang, Wei-Zhang [1 ]
Cheng, Jiasen [1 ]
Luo, Jing [1 ]
Zhuang, Shi-Mei [1 ,2 ]
机构
[1] Sun Yat Sen Univ, Sch Life Sci, State Key Lab Biocontrol, Key Lab Gene Engn,Minist Educ, Guangzhou 510275, Guangdong, Peoples R China
[2] Ctr Canc, State Key Lab Oncol So China, Guangzhou 510060, Guangdong, Peoples R China
基金
中国国家自然科学基金; 英国科研创新办公室;
关键词
curcumin; G2/M arrest; apoptosis; drug resistance; hepatoma cells;
D O I
10.1016/j.febslet.2008.06.048
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
In this study, we showed that curcumin treatment resulted in activation of Chk1-mediated G2 checkpoint, which was associated with the induction of G2/M arrest and the resistance of cancer cells to curcumin-induced apoptosis. Further investigation revealed that inhibition of Chk1 significantly abrogated G2/M arrest and sensitized curcumin-resistant cells to apoptosis via upregulation of Bad and in turn the loss of mitochondrial membrane potential. These results indicate that Chk1-mediated G2/M arrest may serve as a mechanism for curcumin resistance and Chk1 represents a potential target for the reversal of this resistance. Our findings should be helpful for clinical application of curcumin. (c) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
引用
收藏
页码:2689 / 2695
页数:7
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