BACKGROUND/AIM Glioblastoma is a frequent type of brain tumor and is radioresistant. Arsenite, which crosses the blood-brain barrier, shows synergistic effects with radiation in vitro and in vivo. The mechanism… Click to show full abstract
BACKGROUND/AIM Glioblastoma is a frequent type of brain tumor and is radioresistant. Arsenite, which crosses the blood-brain barrier, shows synergistic effects with radiation in vitro and in vivo. The mechanism remains unclear. MATERIALS AND METHODS As synergistic radiosensitization has been reported in p53-deficient cancer cells, radiosensitization was evaluated using the glioblastoma cell line, U87MG-E6, which harbors inactivated p53, in comparison with the cell line, HCT116 p53 (-/-). Radiosensitivity was evaluated using clonogenic assays and detection of abnormal amplification of centrosomes (AAC). RESULTS Synergistic effects of arsenite on radiosensitivity were observed in both cell lines. The radiosensitization induced by arsenite was abolished by N-acetyl-l-cysteine, a reactive oxygen species (ROS) scavenger. Increased radiosensitivity by arsenite was also abolished following knock-down of BRCA2. In addition, the increased radiosensitization by arsenite was correlated with AAC, which was abolished by BRCA2 knock-down. CONCLUSION We conclude that radiosensitization by arsenite is related to ROS and BRCA2 function.
               
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