Oxidative stress and HDACi-induced CHAC1, a downstream effector of the PERK/eIF2a/ATF4 signaling pathway, exacerbate intracellular oxidative stress by depleting GSH, which plays a role in HCC apoptosis induced by oxidative stress and HDACi, as summarized in Figure 8. This evidence concerns the gene ATF4 and hepatocellular carcinoma.