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A Novel Synthetic Compound 3-Amino-3-(4-Fluoro-Phenyl)-1H-Quinoline-2,4-Dione (KR22332) Exerts a Radioprotective Effect via the Inhibition of Mitochondrial Dysfunction and Generation of Reactive Oxygen Species

 Seung Jae Baek  ;  Jae Won Chang  ;  Keun Hyung Park  ;  Garp Yeol Yang  ;  Hye Sook Hwang  ;  Yoon Woo Koh  ;  Young-Sik Jung  ;  Chul-Ho Kim 
 Yonsei Medical Journal, Vol.55(4) : 886-894, 2014 
Journal Title
 Yonsei Medical Journal 
Issue Date
Apoptosis/drug effects ; Apoptosis/physiology ; Cell Line, Tumor ; Cell Survival/drug effects ; Cell Survival/physiology ; Humans ; Keratinocytes/metabolism ; Membrane Potential, Mitochondrial/drug effects ; Membrane Potential, Mitochondrial/physiology ; Radiation-Protective Agents/chemistry ; Radiation-Protective Agents/pharmacology* ; Reactive Oxygen Species/metabolism
3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR22332) ; Radiation induced oral mucositis ; apoptosis ; radioprotection
PURPOSE: Acute side effects of radiation such as oral mucositis are observed in most patients. Although several potential radioprotective agents have been proposed, no effective agent has yet been identified. In this study, we investigated the effectiveness of synthetic compound 3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR22332) as a radioprotective agent. MATERIALS AND METHODS: Cell viability, apoptosis, the generation of reactive oxygen species (ROS), mitochondrial membrane potential changes, and changes in apoptosis-related signaling were examined in human keratinocyte (HaCaT). RESULTS: KR22332 inhibited irradiation-induced apoptosis and intracellular ROS generation, and it markedly attenuated the changes in mitochondrial membrane potential in primary human keratinocytes. Moreover, KR22332 significantly reduced the protein expression levels of ataxia telangiectasia mutated protein, p53, and tumor necrosis factor (TNF)-α compared to significant increases observed after radiation treatment. CONCLUSION: KR22332 significantly inhibited radiation-induced apoptosis in human keratinocytes in vitro, indicating that it might be a safe and effective treatment for the prevention of radiation-induced mucositis.
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1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Kho, Yoon Woo(고윤우)
Baek, Seung Jae(백승재)
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