Synergistic antitumor activity of sorafenib and MG149 in hepatocellular carcinoma cells
Advanced hepatocellular carcinoma (HCC) remains one of the most difficult cancers to treat, highlighting the urgent need for improved therapeutic approaches. Sorafenib is currently the standard first-line treatment for advanced HCC. In our study, we sought to identify a chemical compound that could enhance the efficacy of sorafenib. Screening a specialized chemical library, we discovered that MG149, an inhibitor of histone acetyltransferases targeting the MYST family, demonstrated the most significant synergistic anticancer effect when combined with sorafenib in HCC cells.
The combination of sorafenib and MG149 produced a synergistic anti-proliferative effect by inducing apoptotic cell death. Our findings indicate that this combination exacerbates endoplasmic reticulum (ER) stress, leading to increased cell death in HCC cells rather than enabling adaptive survival. Additionally, the combined treatment significantly elevated levels of unfolded proteins and reactive oxygen species within the cells, further promoting ER stress. Overall, these results suggest that MG149 has the potential to enhance sorafenib’s effectiveness in treating advanced HCC by amplifying cytotoxic ER stress. [BMB Reports 2022; 55(10): 506-511].