Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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Comparison of Anticancer Effects of Histone Deacetylase Inhibitors CG-745 and Suberoylanilide Hydroxamic Acid in Non-small Cell Lung Cancer

  • Hyo Jin Kim (Division of Pulmonary Medicine, Department of Internal Medicine, Wonkwang University School of Medicine) ;
  • Ui Ri An (Division of Pulmonary Medicine, Department of Internal Medicine, Wonkwang University School of Medicine) ;
  • Han Jee Yoon (Division of Pulmonary Medicine, Department of Internal Medicine, Wonkwang University School of Medicine) ;
  • Hyun Lim (Division of Pulmonary Medicine, Department of Internal Medicine, Wonkwang University School of Medicine) ;
  • Ki Eun Hwang (Division of Pulmonary Medicine, Department of Internal Medicine, Wonkwang University School of Medicine) ;
  • Young Suk Kim (Division of Pulmonary Medicine, Department of Internal Medicine, Wonkwang University School of Medicine) ;
  • Hak Ryul Kim (Division of Pulmonary Medicine, Department of Internal Medicine, Wonkwang University School of Medicine)
  • Received : 2024.07.08
  • Accepted : 2025.02.10
  • Published : 2025.04.30
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Abstract

Background: Histone deacetylase (HDAC) inhibition offers potential anticancer effects across diverse cancers due to HDAC's significant role in cancer development and progression. Consequently, we demonstrated the therapeutic efficacy of the novel HDAC inhibitor, CG-745, in comparison with existing inhibitors such as suberoylanilide hydroxamic acid (SAHA) in non-small cell lung cancer (NSCLC) cells. Methods: CG-745's effect on apoptosis and reactive oxygen species (ROS)-dependent mitochondrial dysfunction was investigated using annexin V assay, MitoSoX, and Western blot in human A549 and H460 cells. Additionally, HDAC expression was analyzed through real-time polymerase chain reaction. We also evaluated the inhibitory effect of CG-745 on epithelial-mesenchymal transition (EMT) induced by transforming growth factor β1 (TGF-β1) via Western blot, scratch analysis, and matrigel invasion analysis. Results: Compared to SAHA, CG-745 inhibited cell viability and mRNA expression of HDACs such as HDAC1, HDAC2, HDAC3, and HDAC8. It also induced apoptosis, ROS, and mitochondrial dysfunction in a concentration-dependent manner. CG-745 reversed EMT triggered by TGF-β1 in A549 and H460 cells, and curtailed the migration and invasion enhanced by TGF-β1. CG-745 has demonstrably inhibited EMT and induced apoptosis in NSCLC cells. Conclusion: CG-745 may represent a novel therapeutic strategy for NSCLC treatment.

Keywords

Acknowledgement

This study was supported by a grant from Wonkwang University in 2023.

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