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, Yoonwoo Koh, Young Sik Jung, Chul Ho Kim

Research output: Contribution to journalArticle

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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)-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.

Original languageEnglish
Pages (from-to)886-894
Number of pages9
JournalYonsei medical journal
Volume55
Issue number4
DOIs
Publication statusPublished - 2014 Jan 1

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Reactive Oxygen Species
Radiation-Protective Agents
Keratinocytes
Apoptosis
Mitochondrial Membrane Potential
Radiation
Ataxia Telangiectasia Mutated Proteins
Stomatitis
Mucositis
Radiation Effects
Cell Survival
Tumor Necrosis Factor-alpha
quinoline
Therapeutics
Proteins

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Baek, Seung Jae ; Chang, Jae Won ; Park, Keun Hyung ; Yang, Garp Yeol ; Hwang, Hye Sook ; Koh, Yoonwoo ; Jung, Young Sik ; Kim, Chul Ho. / 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. In: Yonsei medical journal. 2014 ; Vol. 55, No. 4. pp. 886-894.
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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)-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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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. / Baek, Seung Jae; Chang, Jae Won; Park, Keun Hyung; Yang, Garp Yeol; Hwang, Hye Sook; Koh, Yoonwoo; Jung, Young Sik; Kim, Chul Ho.

In: Yonsei medical journal, Vol. 55, No. 4, 01.01.2014, p. 886-894.

Research output: Contribution to journalArticle

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AU - Baek, Seung Jae

AU - Chang, Jae Won

AU - Park, Keun Hyung

AU - Yang, Garp Yeol

AU - Hwang, Hye Sook

AU - Koh, Yoonwoo

AU - Jung, Young Sik

AU - Kim, Chul Ho

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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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