Zebularine-induced apoptosis in Calu-6 lung cancer cells is influenced by ROS and GSH level changes

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• 作者：Bo Ra You (1)
  Woo Hyun Park (1)
  
• 关键词：Zebularine ; DNA methyltransferase ; Apoptosis ; Calu ; 6 ; Glutathione
• 刊名：Tumor Biology
• 出版年：2013
• 出版时间：April 2013
• 年：2013
• 卷：34
• 期：2
• 页码：1145-1153
• 全文大小：454KB
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• 作者单位：Bo Ra You (1)
  Woo Hyun Park (1)
  
  1. Department of Physiology, Medical School, Research Institute for Endocrine Sciences, Chonbuk National University, Jeonju, 561-180, Republic of Korea
  
• ISSN：1423-0380

文摘

Zebularine (Zeb) is a DNA methyltransferase (DNMT) inhibitor that has various biological properties including anti-cancer effect. In the present study, we evaluated the effects of Zeb on the growth and death of Calu-6 lung cancer cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. Zeb inhibited the growth of Calu-6 cells with an IC50 of approximately 150?μM at 72?h in a dose-dependent manner. Zeb induced an S phase arrest of the cell cycle and apoptosis in Calu-6 cells. Pan-caspase inhibitor (Z-VAD) and caspase-8 inhibitor (Z-IETD) significantly rescued some cells from Zeb-induced Calu-6 cell death. In relation to ROS and GSH levels, O2 ?? level was significantly increased in Zeb-treated Calu-6 cells and caspase inhibitors reduced O2 ?? level in these cells. Zeb induced GSH depletion in HeLa cells, which was attenuated by caspase inhibitors. L-buthionine sulfoximine (BSO), a GSH synthesis inhibitor, intensified the apoptotic cell death, ROS level, and GSH depletion in Zeb-treated Calu-6 cells. In addition, BSO increased Bax protein and decreased Bcl-2 protein in Zeb-treated Calu-6 cells. In conclusion, Zeb inhibited the growth of Calu-6 lung cancer cells via cell cycle arrest and caspase-dependent apoptosis and its cell death was influenced by ROS and GSH level changes.