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Wogonin Induces Reactive Oxygen Species Production and Cell Apoptosis in Human Glioma Cancer Cells
Department of Biotechnology, Asia University, Wufeng, Taichung County 41354, Taiwan
Cancer Research Center, Department of Medical Research, Changhua Christian Hospital, Changhua 500, Taiwan
Department of Colorectal Surgery, Buddhist Tzu Chi General Hospital, Taichung Branch, Taichung 427, Taiwan
Graduate Institute of Biotechnology, National Chung Hsing University, Taichung 402, Taiwan
Department of Pharmacology, China Medical University, Taichung 40402, Taiwan
Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung 40402, Taiwan
* Author to whom correspondence should be addressed.
Received: 1 June 2012; in revised form: 6 July 2012 / Accepted: 26 July 2012 / Published: 8 August 2012
Abstract: Glioma is the most common primary adult brain tumor with poor prognosis because of the ease of spreading tumor cells to other regions of the brain. Cell apoptosis is frequently targeted for developing anti-cancer drugs. In the present study, we have assessed wogonin, a flavonoid compound isolated from Scutellaria baicalensis Georgi, induced ROS generation, endoplasmic reticulum (ER) stress and cell apoptosis. Wogonin induced cell death in two different human glioma cells, such as U251 and U87 cells but not in human primary astrocytes (IC 50 > 100 μM). Wogonin-induced apoptotic cell death in glioma cells was measured by propidine iodine (PI) analysis, Tunnel assay and Annexin V staining methods. Furthermore, wogonin also induced caspase-9 and caspase-3 activation as well as up-regulation of cleaved PARP expression. Moreover, treatment of wogonin also increased a number of signature ER stress markers glucose-regulated protein (GRP)-78, GRP-94, Calpain I, and phosphorylation of eukaryotic initiation factor-2α (eIF2α). Treatment of human glioma cells with wogonin was found to induce reactive oxygen species (ROS) generation. Wogonin induced ER stress-related protein expression and cell apoptosis was reduced by the ROS inhibitors apocynin and NAC (N-acetylcysteine). The present study provides evidence to support the fact that wogonin induces human glioma cell apoptosis mediated ROS generation, ER stress activation and cell apoptosis.
Keywords: ROS; apoptosis; wogonin; glioma; ER stress
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Tsai, C.-F.; Yeh, W.-L.; Huang, S.M.; Tan, T.-W.; Lu, D.-Y. Wogonin Induces Reactive Oxygen Species Production and Cell Apoptosis in Human Glioma Cancer Cells. Int. J. Mol. Sci. 2012, 13, 9877-9892.
Tsai C-F, Yeh W-L, Huang SM, Tan T-W, Lu D-Y. Wogonin Induces Reactive Oxygen Species Production and Cell Apoptosis in Human Glioma Cancer Cells. International Journal of Molecular Sciences. 2012; 13(8):9877-9892.
Tsai, Cheng-Fang; Yeh, Wei-Lan; Huang, Ssu Ming; Tan, Tzu-Wei; Lu, Dah-Yuu. 2012. "Wogonin Induces Reactive Oxygen Species Production and Cell Apoptosis in Human Glioma Cancer Cells." Int. J. Mol. Sci. 13, no. 8: 9877-9892.