Marine compounds inhibit growth of multiple myeloma in vitro and in vivo

Normann Steiner, Domenico Ribatti, Wolfgang Willenbacher, Karin Jöhrer, Johann Kern, Christian Marinaccio, Miguel Aracil, Luis F. García-Fernández, Guenther Gastl, Gerold Untergasser, Eberhard Gunsilius

Research output: Contribution to journalArticle

Abstract

Purpose: 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. Experimental Design: 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-myeloma activities 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.

Original languageEnglish
Pages (from-to)8200-8209
Number of pages10
JournalOncotarget
Volume6
Issue number10
Publication statusPublished - 2015

Keywords

  • Angiogenesis
  • CAM
  • Marine drugs
  • Multiple myeloma
  • Xenografts

ASJC Scopus subject areas

  • Oncology

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