Increased Catalase Activity by All-trans Retinoic Acid and Its Effect on Radiosensitivity in Rat Glioma Cells

Jin, Hua; Jeon, Ha Yeun; Park, Woo Yoon; Kim, Won Dong; Ahn, Hee Yul; Yu, Jae Ran

Abstract

PURPOSE: It has been reported that all-trans retinoic acid (ATRA) can inhibit glioma growing in vitro. However, clinical trials with ATRA alone in gliomas revealed modest results. ATRA has been shown to increase radiosensitivity in other tumor types, so combining radiation and ATRA would be one of alternatives to increase therapeutic efficacy in malignant gliomas. Thus, we intended to know the role of catalase, which is induced by ATRA, for radiosensitivity. If radiation-reduced reactive oxygen species (ROS) is removed by catalase, the effect of radiation will be reduced.
MATERIALS AND METHODS
A rat glioma cell line (36B10) was used for this study. The change of catalase activity and radiosensitivity by ATRA, with or without 3-amino-1, 2, 4-triazole (ATZ), a chemical inhibitor of catalase were measured. Catalase activity was measured by the decomposition of H2O2 spectrophotometrically. Radiosensitivity was measured with clonogenic assay. Also ROS was measured using a 2, 7-dichlorofluorescein diacetate spectrophotometrically.
RESULTS
When 36B10 cells were exposed to 10, 25 and 50microM of ATRA for 48 h, the expression of catalase activity were increased with increasing concentration and incubation time of ATRA. Catalase activity was decreased with increasing the concentration of AT (1, 10 mM) dose-dependently. ROS was increased with ATRA and it was augmented with the combination of ATRA and radiation. ATZ decreased ROS production and increased cell survival in combination of ATRA and radiation despite the reduction of catalase.
CONCLUSION
The increase of ROS is one of the reasons for the increased radiosensitivity in combination with ATRA. The catalase that is induced by ATRA doesn`t decrease ROS production and radiosensitivity.