title: Actinopyrone D, a new downregulator of the molecular chaperone GRP78 from Streptomyces sp.
abstract: A new downregulator of the molecular chaperone GRP78, actinopyrone D, was isolated together with a known related compound, PM050463, from Streptomyces sp. RAG92. The molecular formula of actinopyrone D was established as C25H36O4 by high-resolution FAB-MS. NMR spectroscopic analysis revealed the structure of actinopyrone D, which consists of an α-methoxy-γ-pyrone ring and a C17 side chain containing a cis olefin moiety. Actinopyrone D and PM050463 dose-dependently inhibited 2-deoxyglucose-induced luciferase expression in HT1080 human fibrosarcoma cells transfected with a luciferase reporter plasmid containing the GRP78 promoter. Actinopyrone D inhibited GRP78 protein expression and induced cell death under endoplasmic reticulum stress.
authors.affiliation: Faculty of Pharmaceutical Sciences, Department of Medicinal and Life Science, Tokyo University of Science, Chiba, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Hayakawa
authors.affiliation: Faculty of Pharmaceutical Sciences, Department of Medicinal and Life Science, Tokyo University of Science, Chiba, Japan.
authors.forename: Junki
authors.initials: J
authors.lastname: Saito
authors.affiliation: Faculty of Pharmaceutical Sciences, Department of Medicinal and Life Science, Tokyo University of Science, Chiba, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Izawa
authors.affiliation: Biological Information Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shin-ya
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000502:physiology; D005354:Fibrosarcoma / Q000188:drug therapy*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D011753:Pyrones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013302:Streptomyces / Q000378:metabolism*; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D011753:Pyrones; C000595748:actinopyrone D; D008156:Luciferases