Tuberc Respir Dis.  2025 Apr;88(2):342-352. 10.4046/trd.2024.0090.

Comparison of Anticancer Effects of Histone Deacetylase Inhibitors CG-745 and Suberoylanilide Hydroxamic Acid in Non-small Cell Lung Cancer

• Kim HJ
• An UR
• Yoon HJ
• Lim H
• Hwang KE
• Kim YS
• Kim HR

• KMID: 2566189
• DOI: http://doi.org/10.4046/trd.2024.0090

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.

Keyword

CG-745; Apoptosis; Epithelial-Mesenchymal Transition; Non-small Cell Lung Cancer