EIF2AK3 and osteosarcoma: Polyphyllin I at a dose of 1.25 mM inhibited proteasomal CT-like activity in osteosarcoma MG-63, Saos-2 and U-2 OS cells and induced cellular ERS to active the UPR and dispose of accumulated undegraded proteins; BiP expression was upregulated and its mediated PERK-eIF2α-ATF4-GADD153 (CHOP) pathway was activated, and Polyphyllin I inhibited the activity of Bcl-2 and Bcl-xL and promoted the activity of Bax and Bak, which subsequently upregulated caspase-3 and PARP protein expression and triggered apoptosis (Chang et al., 2015).