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. AMB18. The molecular formula of efrapeptin J was established as C(81)H(139)N(18)O(16)(+) 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.
Hayakawa
Yoichi
Y
Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan. hykw@rs.noda.tus.ac.jp
Hattori
Yuki
Y
Kawasaki
Takashi
T
Kanoh
Kaneo
K
Adachi
Kyoko
K
Shizuri
Yoshikazu
Y
Shin-ya
Kazuo
K
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D000091342:Endoplasmic Reticulum Chaperone BiP; D005656:Fungal Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology*; D017930:Genes, Reporter / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D006999:Hypocreales / Q000254:growth & development / Q000378:metabolism*; D008156:Luciferases / Q000037:antagonists & inhibitors / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors* / Q000235:genetics; D054848:Peptaibols; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D000970:Antineoplastic Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; D005656:Fungal Proteins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D054848:Peptaibols; D010455:Peptides; C532990:efrapeptin J; D008156:Luciferases