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

IF 2.5 Q2 RESPIRATORY SYSTEM

Tuberculosis and Respiratory Diseases Pub Date : 2025-04-01 Epub Date: 2025-02-13 DOI:10.4046/trd.2024.0090

Hyo Jin Kim, Ui Ri An, Han Jee Yoon, Hyun Lim, Ki Eun Hwang, Young Suk Kim, Hak Ryul Kim

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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.

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HDAC抑制剂CG-745和SAHA对非小肺癌细胞的抗癌作用比较。

背景：组蛋白去乙酰化酶（HDAC）抑制在多种癌症中具有潜在的抗癌作用，因为HDAC在癌症的发生和进展中起着重要作用。因此，我们证明了新的HDAC抑制剂CG-745在非小细胞肺癌（NSCLC）细胞中的治疗效果，与现有的HDAC抑制剂（如亚酰苯胺羟肟酸（SAHA））相比。方法：采用Annexin V法、MitoSoX法和Western blot法观察CG-745对人A549和H460细胞凋亡和活性氧依赖性线粒体功能障碍的影响。此外，为了确认HDAC的表达，采用实时荧光定量PCR分析。为了通过TGF-β1证实EMT对CG-745的抑制作用，我们进行了Western blot、划痕分析和矩阵侵袭分析。结果：与SAHA相比，CG-745可抑制HDAC1、HDAC2、HDAC3、HDAC8等hdac的细胞活力和mRNA表达。它还以浓度依赖的方式引起细胞凋亡、ROS和线粒体功能障碍。CG-745逆转TGF-β1诱导的A549和H460细胞EMT，抑制TGF-β1增加的迁移和侵袭。CG-745已被证明能抑制EMT并诱导非小细胞肺癌细胞凋亡。结论：CG-745可能成为治疗非小细胞肺癌的一种新的治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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