title: Wogonin induces reactive oxygen species production and cell apoptosis in human glioma cancer cells.
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.
authors.affiliation: Department of Biotechnology, Asia University, Wufeng, Taichung County 41354, Taiwan.
authors.forename: Cheng-Fang
authors.initials: CF
authors.lastname: Tsai
authors.affiliation: Cancer Research Center, Department of Medical Research, Changhua Christian Hospital, Changhua 500, Taiwan.
authors.forename: Wei-Lan
authors.initials: WL
authors.lastname: Yeh
authors.affiliation: 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.
authors.forename: Ssu Ming
authors.initials: SM
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, China Medical University, Taichung 40402, Taiwan.
authors.forename: Tzu-Wei
authors.initials: TW
authors.lastname: Tan
authors.affiliation: Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung 40402, Taiwan.
authors.forename: Dah-Yuu
authors.initials: DY
authors.lastname: Lu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D044950:Flavanones / Q000494:pharmacology*; D005434:Flow Cytometry; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D044950:Flavanones; D017382:Reactive Oxygen Species; D020169:Caspases; C085514:wogonin