Radiat Oncol J.  2012 Jun;30(2):88-95. 10.3857/roj.2012.30.2.88.

Fenofibrate decreases radiation sensitivity via peroxisome proliferator-activated receptor alpha-mediated superoxide dismutase induction in HeLa cells

Affiliations
  • 1Department of Radiation Oncology, Chungbuk National University College of Medicine, Cheongju, Korea. wynpark@chungbuk.ac.kr
  • 2Department of Radiation Oncology, The Catholic University of Korea College of Medicine, Seoul, Korea.
  • 3Department of Environmental and Tropical Medicine, Konkuk University College of Medicine, Chungju, Korea.

Abstract

PURPOSE
The fibrates are ligands for peroxisome proliferator-activated receptor (PPAR) alpha and used clinically as hypolipidemic drugs. The fibrates are known to cause peroxisome proliferation, enhance superoxide dismutase (SOD) expression and catalase activity. The antioxidant actions of the fibrates may modify radiation sensitivity. Here, we investigated the change of the radiation sensitivity in two cervix cancer cell lines in combination with fenofibrate (FF).
MATERIALS AND METHODS
Activity and protein expression of SOD were measured according to the concentration of FF. The mRNA expressions were measured by using real time reverse-transcription polymerase chain reaction. Combined cytotoxic effect of FF and radiation was measured by using clonogenic assay.
RESULTS
In HeLa cells total SOD activity was increased with increasing FF doses up to 30 microM. In the other hand, the catalase activity was increased a little. As with activity the protein expression of SOD1 and SOD2 was increased with increasing doses of FF. The mRNAs of SOD1, SOD2, PPARalpha and PPARgamma were increased with increasing doses of FF. The reactive oxygen species (ROS) produced by radiation was decreased by preincubation with FF. The surviving fractions (SF) by combining FF and radiation was higher than those of radiation alone. In Me180 cells SOD and catalase activity were not increased with FF. Also, the mRNAs of SOD1, SOD2, and PPARalpha were not increased with FF. However, the mRNA of PPARgamma was increased with FF.
CONCLUSION
FF can reduce radiation sensitivity by ROS scavenging via SOD induction in HeLa. SOD induction by FF is related with PPARalpha.

Keyword

Fenofibrate; Radiation sensitivity; Peroxisome proliferator-activated receptor alpha; Superoxide dismutase
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