title: A bromopyrrole-containing diterpene alkaloid from the Okinawan marine sponge Agelas nakamurai activates the insulin pathway in Huh-7 human hepatoma cells by inhibiting protein tyrosine phosphatase 1B.
abstract: Agelasine G (1), a known bromine-containing diterpene alkaloid, was isolated as a new type of protein tyrosine phosphatase (PTP) 1B inhibitor together with ageline B (2), an inactive debromo-derivative of 1, from the marine sponge Agelas nakamurai collected at Iriomote Island in Okinawa, Japan. Further biological evaluations revealed that compound 1 exhibited selective inhibitory activity against PTP1B over T-cell PTP and CD45 phosphatase. Compound 1 also enhanced the insulin-stimulated phosphorylation levels of Akt in Huh-7 cells more strongly than compound 2. The results obtained in this study suggest that compound 1 activates the insulin signaling pathway by inhibiting PTP1B activity.
authors.affiliation: Department of Natural Product Chemistry, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan. Electronic address: yamazaki@tohoku-mpu.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamazaki
authors.affiliation: Department of Clinical Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan. Electronic address: syu-kan@tohoku-mpu.ac.jp.
authors.forename: Syu-Ichi
authors.initials: SI
authors.lastname: Kanno
authors.affiliation: Department of Natural Product Chemistry, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan; Faculty of Fisheries and Marine Science, Sam Ratulangi University, Kampus Bahu, Manado 95115, Indonesia.
authors.forename: Delfly B
authors.initials: DB
authors.lastname: Abdjul
authors.affiliation: Department of Natural Product Chemistry, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Namikoshi
mesh_terms: D047230:Agelas / Q000737:chemistry* / Q000378:metabolism; D000470:Alkaloids / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007564:Japan; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011758:Pyrroles / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000470:Alkaloids; D004224:Diterpenes; D004791:Enzyme Inhibitors; D007328:Insulin; D011758:Pyrroles; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Agelasine G; Ageline B; Inhibitor; Marine sponge; Protein tyrosine phosphatase 1B