title: Increased expression of antioxidant enzymes in radioresistant variant from U251 human glioblastoma cell line.
abstract: 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.
authors.affiliation: Laboratory of Cell Biology, Korea Institute of Radiological Medical Sciences, Seoul, Korea.
authors.forename: Hyung-Chahn
authors.initials: HC
authors.lastname: Lee
authors.forename: Dae-Won
authors.initials: DW
authors.lastname: Kim
authors.forename: Kyung-Yong
authors.initials: KY
authors.lastname: Jung
authors.forename: In-Chul
authors.initials: IC
authors.lastname: Park
authors.forename: Myung-Jin
authors.initials: MJ
authors.lastname: Park
authors.forename: Mi-Suk
authors.initials: MS
authors.lastname: Kim
authors.forename: Sang-Hyeok
authors.initials: SH
authors.lastname: Woo
authors.forename: Chang-Hun
authors.initials: CH
authors.lastname: Rhee
authors.forename: Heon
authors.initials: H
authors.lastname: Yoo
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Seok-Il
authors.initials: SI
authors.lastname: Hong
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology* / Q000528:radiation effects; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D005909:Glioblastoma / Q000201:enzymology* / Q000532:radiotherapy; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000528:radiation effects*; D011836:Radiation Tolerance / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D002945:Cisplatin