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

2 Citations (Scopus)

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

Fingerprint

Multiple Myeloma
Porifera
Gelatin
Growth
Cell Line
Conditioned Culture Medium
Heterografts
Bone Marrow Cells
Pharmaceutical Preparations
Chickens
Blood Cells
Neoplasms
Flow Cytometry
Research Design
Embryonic Structures
Endothelial Cells
Fluorescence
Bone Marrow
Enzyme-Linked Immunosorbent Assay
Apoptosis

Keywords

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

ASJC Scopus subject areas

  • Oncology

Cite this

Steiner, N., Ribatti, D., Willenbacher, W., Jöhrer, K., Kern, J., Marinaccio, C., ... Gunsilius, E. (2015). Marine compounds inhibit growth of multiple myeloma in vitro and in vivo. Oncotarget, 6(10), 8200-8209.

Marine compounds inhibit growth of multiple myeloma in vitro and in vivo. / Steiner, Normann; Ribatti, Domenico; Willenbacher, Wolfgang; Jöhrer, Karin; Kern, Johann; Marinaccio, Christian; Aracil, Miguel; García-Fernández, Luis F.; Gastl, Guenther; Untergasser, Gerold; Gunsilius, Eberhard.

In: Oncotarget, Vol. 6, No. 10, 2015, p. 8200-8209.

Research output: Contribution to journalArticle

Steiner, N, Ribatti, D, Willenbacher, W, Jöhrer, K, Kern, J, Marinaccio, C, Aracil, M, García-Fernández, LF, Gastl, G, Untergasser, G & Gunsilius, E 2015, 'Marine compounds inhibit growth of multiple myeloma in vitro and in vivo', Oncotarget, vol. 6, no. 10, pp. 8200-8209.
Steiner N, Ribatti D, Willenbacher W, Jöhrer K, Kern J, Marinaccio C et al. Marine compounds inhibit growth of multiple myeloma in vitro and in vivo. Oncotarget. 2015;6(10):8200-8209.
Steiner, Normann ; Ribatti, Domenico ; Willenbacher, Wolfgang ; Jöhrer, Karin ; Kern, Johann ; Marinaccio, Christian ; Aracil, Miguel ; García-Fernández, Luis F. ; Gastl, Guenther ; Untergasser, Gerold ; Gunsilius, Eberhard. / Marine compounds inhibit growth of multiple myeloma in vitro and in vivo. In: Oncotarget. 2015 ; Vol. 6, No. 10. pp. 8200-8209.
@article{b83635ec46a24e5a9c4207e3343b87e8,
title = "Marine compounds inhibit growth of multiple myeloma in vitro and in vivo",
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.",
keywords = "Angiogenesis, CAM, Marine drugs, Multiple myeloma, Xenografts",
author = "Normann Steiner and Domenico Ribatti and Wolfgang Willenbacher and Karin J{\"o}hrer and Johann Kern and Christian Marinaccio and Miguel Aracil and Garc{\'i}a-Fern{\'a}ndez, {Luis F.} and Guenther Gastl and Gerold Untergasser and Eberhard Gunsilius",
year = "2015",
language = "English",
volume = "6",
pages = "8200--8209",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "10",

}

TY - JOUR

T1 - Marine compounds inhibit growth of multiple myeloma in vitro and in vivo

AU - Steiner, Normann

AU - Ribatti, Domenico

AU - Willenbacher, Wolfgang

AU - Jöhrer, Karin

AU - Kern, Johann

AU - Marinaccio, Christian

AU - Aracil, Miguel

AU - García-Fernández, Luis F.

AU - Gastl, Guenther

AU - Untergasser, Gerold

AU - Gunsilius, Eberhard

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - Angiogenesis

KW - CAM

KW - Marine drugs

KW - Multiple myeloma

KW - Xenografts

UR - http://www.scopus.com/inward/record.url?scp=84928381190&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928381190&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:84928381190

VL - 6

SP - 8200

EP - 8209

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 10

ER -