Development of Antioxidant COX-2 Inhibitors as Radioprotective Agents for Radiation Therapy-A Hypothesis-Driven Review.
Radiation therapy (RT) evolved to be a primary treatment modality for cancer patients. Unfortunately, the cure or relief of symptoms is still accompanied by radiation-induced side effects with severe acute and late pathophysiological consequences. Inhibitors of cyclooxygenase-2 (COX-2) are potentially useful in this regard because radioprotection of normal tissue and/or radiosensitizing effects on tumor tissue have been described for several compounds of this structurally diverse class. This review aims to substantiate the hypothesis that antioxidant COX-2 inhibitors are promising radioprotectants because of intercepting radiation-induced oxidative stress and inflammation in normal tissue, especially the vascular system. For this, literature reporting on COX inhibitors exerting radioprotective and/or radiosensitizing action as well as on antioxidant COX inhibitors will be reviewed comprehensively with the aim to find cross-points of both and, by that, stimulate further research in the field of radioprotective agents.
Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, Dresden D-01328, Germany. m.laube@hzdr.de.
Markus
M
Laube
Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, Dresden D-01328, Germany. t.kniess@hzdr.de.
Torsten
T
Kniess
Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, Dresden D-01328, Germany. j.pietzsch@hzdr.de.|Department of Chemistry and Food Chemistry, Technische Universität Dresden, Dresden D-01062, Germany. j.pietzsch@hzdr.de.
Jens
J
Pietzsch
COX-2 inhibitors (COXIBs); cyclooxygenases; nonsteroidal anti-inflammatory drugs (NSAIDS); normal tissue; oxidative stress; radiation-induced vascular dysfunction; radioprotection; radiosensitization; reactive oxygen/nitrogen species; tumor models