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

作者：Baek Seung Jae; Chang Jae Won; Park Keun Hyung; Yang Garp Yeol; Hwang Hye Sook; Koh Yoon Woo; Jung Young Sik; Kim Chul Ho^*

来源：Yonsei Medical Journal, 2014, 55(4): 886-894.

DOI：10.3349/ymj.2014.55.4.886

• Radiation induced oral mucositis
• 3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR22332)
• 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-pheny1)-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)-alpha 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.

• 出版日期2014-7-1