Efrapeptin J, a new down-regulator of the molecular chaperone GRP78 from a marine Tolypocladium sp.

A new down-regulator of the molecular chaperone GRP78, efrapeptin J, was isolated from a marine fungus, Tolypocladium sp. AMB 18. The molecular formula of efrapeptin J was established as C81H139N18O16+ by high-resolution FAB-MS. The structure was elucidated to be a linear pentadecapeptide containing a hexahydropyrrolo[1,2-a]pyrimidinium moiety by NMR and MS analyses. Efrapeptins F, G and J dose-dependently inhibited 2-deoxyglucose-induced luciferase expression in HT1080 human fibrosarcoma cells transfected with a luciferase reporter plasmid containing the GRP78 promoter. Efrapeptin J also inhibited the protein expression of GRP78 in HT1080 cells and MKN-74 human gastric cancer cells. Efrapeptin J induced cell death in HT1080 cells under endoplasmic reticulum stress.