title: 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.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Otolaryngology-Head and Neck Surgery, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors: Seung Jae
authors: SJ
authors: Baek
authors: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea. ; Center for Cell Death Regulating Biodrug, School of Medicine, Ajou University, Suwon, Korea.
authors: Jae Won
authors: JW
authors: Chang
authors: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea. ; Center for Cell Death Regulating Biodrug, School of Medicine, Ajou University, Suwon, Korea.
authors: Keun Hyung
authors: KH
authors: Park
authors: Bio-Organic Science Division, Korea Research Institute of Chemical Technology, Daejeon, Korea.
authors: Garp Yeol
authors: GY
authors: Yang
authors: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea. ; Center for Cell Death Regulating Biodrug, School of Medicine, Ajou University, Suwon, Korea.
authors: Hye Sook
authors: HS
authors: Hwang
authors: Department of Otorhinolaryngology, Yonsei Head and Neck Cancer Clinic, Yonsei University College of Medicine, Seoul, Korea.
authors: Yoon Woo
authors: YW
authors: Koh
authors: Bio-Organic Science Division, Korea Research Institute of Chemical Technology, Daejeon, Korea.
authors: Young-Sik
authors: YS
authors: Jung
authors: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea. ostium@ajou.ac.kr; Center for Cell Death Regulating Biodrug, School of Medicine, Ajou University, Suwon, Korea.
authors: Chul-Ho
authors: CH
authors: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D011837:Radiation-Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species
keywords: 3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR22332); Radiation induced oral mucositis; apoptosis; radioprotection