Zebularine inhibits the growth of HeLa cervical cancer cells via cell cycle arrest and caspase-dependent apoptosis
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- 作者：Bo Ra You (1)
Woo Hyun Park (1) parkwh71@chonbuk.ac.kr - 关键词：Zebularine – ; DNA methyltransferase – ; Apoptosis – ; HeLa – ; Caspase
- 刊名：Molecular Biology Reports
- 出版年：2012
- 出版时间：October 2012
- 年：2012
- 卷：39
- 期：10
- 页码：9723-9731
- 全文大小：557.1 KB
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- ISSN：1573-4978
文摘
Zebularine (Zeb) as a DNA methyltrasferase (DNMT) inhibitor has various cellular effects such as cell growth inhibition and apoptosis. In the present study, we evaluated the effects of Zeb on the growth and death of HeLa cervical cancer cells. Zeb inhibited the growth of HeLa cells with an IC50 of approximately 130 μM at 72 h in a dose-dependent manner. DNA flow cytometric analysis indicated that Zeb induced an S phase arrest of the cell cycle, which was accompanied by the increased levels of cdk2 and cyclin A proteins. This agent also induced apoptosis, which was accompanied by the loss of mitochondrial membrane potential (Ψm), PARP-1 cleavage and the activation of caspase-3, -8 and -9. All of the tested caspase inhibitors significantly rescued some cells from Zeb-induced HeLa cell death. In relation to reactive oxygen species (ROS) and glutathione (GSH) levels, O2•− level was significantly increased in 100 μM Zeb-treated HeLa cells and caspase inhibitors reduced O2•− level in these cells. Zeb induced GSH depletion in HeLa cells, which was attenuated by caspase inhibitors. In conclusion, this is the first report that Zeb inhibited the growth of HeLa cells via cell cycle arrest and apoptosis.