Piperlongumine Inhibits Migration of Glioblastoma Cells via Activation of ROS-Dependent p38 and JNK Signaling Pathways
Autor: | Xiao Qiang Xie, Yong Chen, Ju Mei Liu, Di Liu, Qian Rong Liu, Feng Pan, Xiao Qian Chen, Xin Xin Xiong, Xin Yao Qiu, Shang Bin Yu |
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Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Aging
Article Subject MAP Kinase Signaling System p38 mitogen-activated protein kinases Biology p38 Mitogen-Activated Protein Kinases Biochemistry chemistry.chemical_compound Cyclin D1 NF-KappaB Inhibitor alpha Cell Movement Cell Line Tumor Humans lcsh:QH573-671 Piperlongumine Cell Proliferation Cell Nucleus Cell growth lcsh:Cytology JNK Mitogen-Activated Protein Kinases NF-kappa B Dioxolanes Cell migration Cell Biology General Medicine Cell biology Enzyme Activation Protein Transport IκBα chemistry Cell culture Astrocytes Cancer cell I-kappa B Proteins Cell Migration Assays Glioblastoma Reactive Oxygen Species Research Article |
Zdroj: | Oxidative Medicine and Cellular Longevity, Vol 2014 (2014) Oxidative Medicine and Cellular Longevity |
ISSN: | 1942-0900 |
DOI: | 10.1155/2014/653732 |
Popis: | Piperlongumine (PL) is recently found to kill cancer cells selectively and effectively via targeting reactive oxygen species (ROS) responses. To further explore the therapeutic effects of PL in cancers, we investigated the role and mechanisms of PL in cancer cell migration. PL effectively inhibited the migration of human glioma (LN229 or U87 MG) cells but not normal astrocytes in the scratch-wound culture model. PL did not alter EdU+-cells and cdc2, cdc25c, or cyclin D1 expression in our model. PL increased ROS (measured by DCFH-DA), reduced glutathione, activated p38 and JNK, increased IκBα, and suppressed NFκB in LN229 cells after scratching. All the biological effects of PL in scratched LN229 cells were completely abolished by the antioxidant N-acetyl-L-cysteine (NAC). Pharmacological administration of specific p38 (SB203580) or JNK (SP600125) inhibitors significantly reduced the inhibitory effects of PL on LN229 cell migration and NFκB activity in scratch-wound and/or transwell models. PL prevented the deformation of migrated LN229 cells while NAC, SB203580, or SP600125 reversed PL-induced morphological changes of migrated cells. These results suggest potential therapeutic effects of PL in the treatment and prevention of highly malignant tumors such as glioblastoma multiforme (GBM) in the brain by suppressing tumor invasion and metastasis. |
Databáze: | OpenAIRE |
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