Abrogation of G2/M arrest sensitizes curcumin-resistant hepatoma cells to apoptosis
Abrogation of G2/M arrest sensitizes curcumin-resistant hepatoma cells to apoptosis
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DOI：
10.1016/j.febslet.2008.06.048
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发表时间：
2008-08-06
期刊：
影响因子：
3.5
通讯作者：
Zhuang, Shi-Mei
中科院分区：
文献类型：
--
作者：
Wang, Wei-Zhang;Cheng, Jiasen;Zhuang, Shi-Mei
在这项研究中，我们发现姜黄素处理导致Chk 1介导的G2检查点激活，这与诱导G2/M期阻滞和癌细胞对姜黄素诱导的凋亡的抵抗有关。进一步的研究表明，抑制Chk 1显着废除G2/M期阻滞和敏感的姜黄素耐药细胞凋亡通过上调Bad，进而损失线粒体膜电位。这些结果表明，Chk 1介导的G2/M期阻滞可能是姜黄素耐药的一种机制，Chk 1是逆转这种耐药的潜在靶点。本研究为姜黄素的临床应用提供了参考。(c)2008年欧洲生物化学学会联合会。由Elsevier B出版。V.保留所有权利。
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.