Increased expression of antioxidant enzymes in radioresistant variant from U251 human glioblastoma cell line.
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.
Lee
Hyung-Chahn
HC
Laboratory of Cell Biology, Korea Institute of Radiological Medical Sciences, Seoul, Korea.
Kim
Dae-Won
DW
Jung
Kyung-Yong
KY
Park
In-Chul
IC
Park
Myung-Jin
MJ
Kim
Mi-Suk
MS
Woo
Sang-Hyeok
SH
Rhee
Chang-Hun
CH
Yoo
Heon
H
Lee
Seung-Hoon
SH
Hong
Seok-Il
SI
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
D000975:Antioxidants; D017382:Reactive Oxygen Species; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D002945:Cisplatin