HDAC Inhibitor, CG-745 Inhibit EMT and Induce Apoptosis in Non-small Cell Lung Cancer

<bold>Backgroud:</bold> Histone deacetylase (HDAC) inhibition offers the potential for anti-cancer effects in a variety of cancers, since HDAC plays an important role in cancer development and progression. Thus, we demonstrated the therapeutic efficacy of the new HDAC inhibitor, CG200745, in comparison with existing HDAC inhibitors, such as suberoylanilide hydroxamic acid (SAHA) in non-small lung cancer cells. <bold>Methods:</bold> The effect of CG200745 on apoptosis and reactive oxygen species (ROS) dependent mitochondrial dysfunction in human A549 and H460 cells was investigated by Annexin V assay, MitoSoX and Western blot. Also, to confirm HDAC expression, it was analyzed using real-time PCR. To confirm the inhibitory effect of EMT on CG200745 by TGF- beta 1, Western blot, scratch analysis, and matrigel invasion analysis were performed. <bold>Results:</bold> Compared to SAHA, CG200745 inhibited cell viability and mRNA expression of HDACs such as HDAC1, HDAC2, HDAC3 and HDAC8. It also caused apoptosis, ROS and mitochondrial dysfunction in a concentration-dependent manner. CG200745 reversed EMT induced by TGF- beta 1 in human A549 and H460 cells, and inhibited migration and invasion increased by TGF- beta 1. CG200745 has been shown to inhibit EMT and induce apoptosis in NSCLC cells. <bold>Conclusion:</bold> It suggests that CG200745 could be a new treatment strategy for treatment of NSCLC.