title: Marine compounds inhibit growth of multiple myeloma in vitro and in vivo.
abstract: OBJECTIVE
  The prognosis of patients with multiple myeloma (MM) is still dismal despite recent improvements achieved by introducing new therapeutic agents. However, there remains an urgent need for progress in myeloma drug development. We here show that novel marine-derived compounds can exert potent anti-myeloma activity.
  
  
  METHODS
  Nine marine-derived compounds were applied at low nM concentrations (0.1-100 nM) to MM cell lines (OPM-2, NCI-H929, U266, RPMI-8226), to primary human myeloma cells and to peripheral blood mononuclear cells. Apoptosis was determined by flow cytometry. In addition, eGFP-transgenic MM cell lines growing with mesenchymal cells from bone marrow were used to visualize tumors by fluorescence stereomicroscopy. Anti-myelomaactivities were studied in vitro in 3D spheroids and in vivo in myeloma xenografts on chicken embryos. Tumor size was analyzed by measuring GFP content with a GFP ELISA. Anti-angiogenic activities of compounds were tested in an in vivo gelatin sponge assay with conditioned media from primary bone marrow-derived endothelial cells.
  
  
  RESULTS
  We identified a subset of marine compounds with strong anti-myeloma activity in vitro and in vivo. Moreover, some of the compounds inhibited myeloma-related angiogenesis in the in vivo gelatin sponge assay. They merit further drug development to improve treatment options for MM.
authors: Laboratory for Tumor Biology & Angiogenesis, Innsbruck Medical University, Innsbruck, Austria.|Department of Internal Medicine V, Innsbruck Medical University, Innsbruck, Austria.
authors: Normann
authors: N
authors: Steiner
authors: Department of Basic Medical Sciences, Neurosciences, and Sensory Organs, University of Bari Medical School, Bari, Italy.|National Cancer Institute "Giovanni Paolo II", Bari, Italy.
authors: Domenico
authors: D
authors: Ribatti
authors: Department of Internal Medicine V, Innsbruck Medical University, Innsbruck, Austria.|Oncotyrol GmbH, Innsbruck, Austria.
authors: Wolfgang
authors: W
authors: Willenbacher
authors: Tyrolean Cancer Research Institute, Innsbruck, Austria.
authors: Karin
authors: K
authors: Jöhrer
authors: Laboratory for Tumor Biology & Angiogenesis, Innsbruck Medical University, Innsbruck, Austria.|Oncotyrol GmbH, Innsbruck, Austria.
authors: Johann
authors: J
authors: Kern
authors: Department of Basic Medical Sciences, Neurosciences, and Sensory Organs, University of Bari Medical School, Bari, Italy.
authors: Christian
authors: C
authors: Marinaccio
authors: PharmaMar R&D, Colmenar Viejo, Madrid, Spain.
authors: Miguel
authors: M
authors: Aracil
authors: PharmaMar R&D, Colmenar Viejo, Madrid, Spain.
authors: Luis F
authors: LF
authors: García-Fernández
authors: Department of Internal Medicine V, Innsbruck Medical University, Innsbruck, Austria.
authors: Guenther
authors: G
authors: Gastl
authors: Laboratory for Tumor Biology & Angiogenesis, Innsbruck Medical University, Innsbruck, Austria.|Tyrolean Cancer Research Institute, Innsbruck, Austria.
authors: Gerold
authors: G
authors: Untergasser
authors: Laboratory for Tumor Biology & Angiogenesis, Innsbruck Medical University, Innsbruck, Austria.|Department of Internal Medicine V, Innsbruck Medical University, Innsbruck, Austria.
authors: Eberhard
authors: E
authors: Gunsilius
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D059001:Aquatic Organisms / Q000737:chemistry*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002642:Chick Embryo; D004354:Drug Screening Assays, Antitumor; D064593:Heterografts; D006801:Humans; D009101:Multiple Myeloma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D018874:Spheroids, Cellular; D014162:Transfection
chemical_list: D020533:Angiogenesis Inhibitors; D001688:Biological Products
keywords: CAM; angiogenesis; marine drugs; multiple myeloma; xenografts