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

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)-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.