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  • Title: Zebularine-induced apoptosis in Calu-6 lung cancer cells is influenced by ROS and GSH level changes.
    Author: You BR, Park WH.
    Journal: Tumour Biol; 2013 Apr; 34(2):1145-53. PubMed ID: 23338718.
    Abstract:
    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.
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