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

• Published in: Yonsei medical journal Vol. 55; no. 4; pp. 886 - 894
• Main Authors: Baek, Seung Jae, Chang, Jae Won, Park, Keun Hyung, Yang, Garp Yeol, Hwang, Hye Sook, Koh, Yoon Woo, Jung, Young-Sik, Kim, Chul-Ho
• Format: Journal Article
• Language: English
• Published: Korea (South) Yonsei University College of Medicine 01.07.2014; 연세대학교의과대학
• Subjects: 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; Original; Radiation-Protective Agents - chemistry; Radiation-Protective Agents - pharmacology; Reactive Oxygen Species - metabolism; 의학일반; Radiation induced oral mucositis; apoptosis; radioprotection; 3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR22332)
• ISSN: 0513-5796; 1976-2437
• DOI: 10.3349/ymj.2014.55.4.886

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. 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). 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. 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.