Yuan YJ et al. (2023) reported that acetylshikonin (10 mM for 24 h) inhibited the proliferation of ESCC cells in vitro at KYSE450, TE10, KYSE180, KYSE510, EC109, EC9706 and blocked cell cycle in G1/S phase. Additional experiments in vitro and in vivo revealed that increased apoptosis in KYSE180 and KYSE450 cells was accompanied with upregulation of BIP, ATF3, ATF4, p-eIF2α, and XBP-1 and was attenuated by CHOP knockdown and the PERK inhibitor GSK2606414, which demonstrated that acetylshikonin inhibits ESCC through activation of the PERK/eIF2α/CHOP axis. This evidence concerns the gene ATF4 and esophageal squamous cell carcinoma.