Ebselen abrogates TNFα induced pro-inflammatory response in glioblastoma

详细信息    查看全文

• 作者：Richa Tewari ; Vivek Sharma ; Nitin Koul ; Abhishek Ghosh ; Christy Joseph ; Ugir Hossain Sk ; Ellora Sen
• 关键词：Glioblastoma ; TNFα ; Ebselen ; Pro-inflammatory cytokines
• 刊名：Molecular Oncology
• 出版年：2009
• 出版时间：February 2009
• 年：2009
• 卷：3
• 期：1
• 页码：77-83
• 全文大小：1161 K

文摘

We investigated the pro-inflammatory response mediated by TNFα in glioblastoma and whether treatment with organoselenium Ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]one) can affect TNFα induced inflammatory response. Exposure to TNFα increased the expression of pro-inflammatory mediator interleukin IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and cyclooxygenase (COX-2). Treatment with Ebselen abrogated TNFα induced increase in pro-inflammatory mediators. Ebselen not only abrogated TNFα induced enhanced invasiveness of glioma cells by down-regulating matrix metallo proteinase (MMP-9) and urokinase plasminogen (uPa) activity, but also inhibited glioma cell migration. Treatment with Ebselen also down-regulated the enhanced ROS production of TNFα treated glioma cells. In addition, Ebselen induced DNA damage repair signaling response in glioma cells both in the presence and absence of TNFα. These studies indicate that together with its known ability to sensitize glioma cell to TNFα induced apoptosis, Ebselen can overcome TNFα induced pro-inflammatory mediators to prevent a build up of a deleterious pro-inflammatory tumor microenvironment.