Increased expression of antioxidant enzymes in radioresistant variant from U251 human glioblastoma cell line

Int J Mol Med. 2004 Jun;13(6):883-7.


Glioblastoma is one of the most radioresistant tumors. Exposure of cells to ionizing radiation leads to formation of reactive oxygen species (ROS) that are associated with radiation-induced cytotoxicity. ROS scavengers, therefore, are one of the important factors in protecting cells against ROS injury during ionizing radiation exposure. In the present study, we isolated and established a radioresistant variant clone (RRC) from U251 human glioblastoma cell line and investigated the potential role of antioxidant enzymes in radioresistance of the glioblastoma cell line. RRC showed a higher radioresistance than the parent cell line as measured by clonogenic survival assay and showed delayed G2/M arrest. Antioxidant enzymes, such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPX), glutathione reductase (GR), were activated up to 5-fold in RRC compared to the parent cells after radiation. In addition, RRC also had cross-resistance to the antitumor agent cisplatin. Therefore, radioresistance and cross-resistance to chemotherapeutic agent in RRC might be due to the highly coordinated activation of antioxidant enzymes rather than a single enzyme alone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / metabolism*
  • Catalase / metabolism
  • Cell Survival / physiology*
  • Cell Survival / radiation effects
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm / physiology
  • Glioblastoma / enzymology*
  • Glioblastoma / radiotherapy
  • Glutathione Peroxidase / metabolism
  • Glutathione Reductase / metabolism
  • Humans
  • Oxidative Stress / radiation effects*
  • Radiation Tolerance / physiology
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / metabolism*
  • Tumor Cells, Cultured


  • Antioxidants
  • Reactive Oxygen Species
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione Reductase
  • Cisplatin