Studies have shown that esculin can trigger ER stress, thereby increasing the level of PERK protein and activating the PERK-eIF2α-CHOP and PERK-Nrf2-HO-1 signaling pathways(22); these pathways jointly promote apoptosis and ferroptosis of colorectal cancer cells in vitro and in vivo; ER stress-induced apoptosis in chronic cerebral hypoperfusion (CCH) is associated with the IRE1α/TRAF2/ASK1/JNK signaling pathway; Licochalcone A (LicA) can induce apoptosis in endometrial cancer (EMC) cells through the GRP78-mediated ER-stress pathway. This evidence concerns the gene MAP3K5 and columnar cell hyperplasia of the breast.