Oncotarget

Research Papers:

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 and Eberhard Gunsilius _

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Oncotarget. 2015; 6:8200-8209. https://doi.org/10.18632/oncotarget.3362

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Abstract

Normann Steiner1,2, Domenico Ribatti4,5, Wolfgang Willenbacher2,7, Karin Jöhrer3, Johann Kern1,7, Christian Marinaccio4, Miguel Aracil6, Luis F. García-Fernández6, Guenther Gastl2, Gerold Untergasser1,3,* and Eberhard Gunsilius1,2,*

1 Laboratory for Tumor Biology & Angiogenesis, Innsbruck Medical University, Innsbruck, Austria

2 Department of Internal Medicine V, Innsbruck Medical University, Innsbruck, Austria

3 Tyrolean Cancer Research Institute, Innsbruck, Austria

4 Department of Basic Medical Sciences, Neurosciences, and Sensory Organs, University of Bari Medical School, Bari, Italy

5 National Cancer Institute “Giovanni Paolo II”, Bari, Italy

6 PharmaMar R&D, Colmenar Viejo, Madrid, Spain

7 Oncotyrol GmbH, Innsbruck, Austria

* These authors contributed equally to this work

Correspondence to:

Eberhard Gunsilius, email:

Keywords: Marine drugs, Angiogenesis, Multiple Myeloma, CAM, Xenografts

Received: December 02, 2014 Accepted: January 15, 2015 Published: January 31, 2015

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-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.


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