title: Curcumin enhances the radiosensitivity of U87 cells by inducing DUSP-2 up-regulation.
abstract: OBJECTIVE
  Glioblastoma multiforme (GBM), an aggressive primary brain tumor, is radioresistant and recurs despite aggressive surgery, chemotherapy, and radiotherapy. Curcumin as a potential radiosensitizer has received extensive attention in cancer treatment. To explore an effectiveness of this radiosensitizer for GBM treatment, we evaluated the radiosensitizing effect of curcumin and investigated its potential molecular mechanisms in the human glioma cell line U87.
  
  
  METHODS
  The cytotoxic effects of curcumin on U87 cells were evaluated using the Cell Counting Kit-8 assay, and the radiosensitivity of U87 cells treated with curcumin was accessed by colony information assay. The effects of curcumin on cell proliferation and cell cycle regulation were determined using the 5-ethynyl-2-deoxyuridine incorporation assay and flow cytometry, respectively. Western blotting was applied to determine the effects of curcumin on protein expression of dual-specificity phosphatase-2 (DUSP-2), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) as well as phosphorylated ERK and JNK.
  
  
  RESULTS
  Curcumin significantly inhibited the proliferation of U87 cells in a dose-and time-dependent manner. Curcumin treatment at the concentrations of 5 µM and 10 M could significantly reduce the clonogenic activity and enhance the radiosensitivity of U87 cells with sensitive enhancement ratios (SERs) of 1.71 and 4.65, respectively. Curcumin resulted in G2/M cell cycle arrest in U87 cells, which were radiosensitive. Pre-treatment of U87-MG cells with 5 µM curcumin enhanced radiation-induced cell proliferation inhibition and apoptosis. Furthermore, we observed that curcumin increased DUSP-2 protein expression and decreased the phosphorylation of ERK and JNK.
  
  
  CONCLUSIONS
  Our results suggest that low-dose curcumin may enhance the radiosensitivity of human glioma U87 cells in vitro by inducing G2/M cell cycle arrest through up-regulation of DUSP-2 expression and inhibition of ERK and JNK phosphorylation.
authors: Department of Neurosurgery, Wuxi People's Hospital, Nanjing Medical University, Wuxi, China.
authors: Yu
authors: Y
authors: Qian
authors: Jianfen
authors: J
authors: Ma
authors: Xiaoyi
authors: X
authors: Guo
authors: Jun
authors: J
authors: Sun
authors: Yongtao
authors: Y
authors: Yu
authors: Boqiang
authors: B
authors: Cao
authors: Lei
authors: L
authors: Zhang
authors: Xiaopeng
authors: X
authors: Ding
authors: Jin
authors: J
authors: Huang
authors: Jun Fei
authors: JF
authors: Shao
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D054641:Dual Specificity Phosphatase 2 / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D015854:Up-Regulation / Q000187:drug effects* / Q000528:radiation effects
chemical_list: D000970:Antineoplastic Agents; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D054641:Dual Specificity Phosphatase 2; D003474:Curcumin