Shikonin at 1.5 μM significantly upregulated BiP protein expression in CRC HCT-116 and HCT-15 cells, activated the ERS-mediated PERK/elF2α/ATF4/CHOP and IRE1α/JNK signaling pathways, lowered the expression of Bcl-2 and enhanced the expression of caspase-3/9 to trigger apoptosis in relevant cells; the same results were obtained after 3 mg/kg shikonin in HCT-116 and HCT-15 cell-grown rhabdoid mice (Qi et al., 2022). The gene discussed is ATF4; the disease is colorectal carcinoma.