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Mar Drugs. 2018 May 20;16(5). pii: E172. doi: 10.3390/md16050172.

Anti-Tumorigenic and Anti-Metastatic Activity of the Sponge-Derived Marine Drugs Aeroplysinin-1 and Isofistularin-3 against Pheochromocytoma In Vitro.

Author information

1
Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. Nicole.bechmann@uniklinikum-dresden.de.
2
Institute of Experimental Physics, TU Bergakademie Freiberg, Leipziger 23, 09599 Freiberg, Germany. Hermann.Ehrlich@physik.tu-freiberg.de.
3
Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. Graeme.eisenhofer@uniklinikum-dresden.de.
4
Department of Medicine III, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. Graeme.eisenhofer@uniklinikum-dresden.de.
5
BromMarin GmbH, Wernerstraße 1, 09599 Freiberg, Germany. Andre.ehrlich@brommarin.de.
6
BromMarin GmbH, Wernerstraße 1, 09599 Freiberg, Germany. Stephan.meschke@brommarin.de.
7
Department of Medicine III, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. Christian.ziegler@uniklinikum-dresden.de.
8
Department of Medicine III, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. Stefan.bornstein@uniklinikum-dresden.de.
9
Center for Regenerative Therapies Dresden, Technical University Dresden, Fetscherstrasse 105, 01307 Dresden, Germany. Stefan.bornstein@uniklinikum-dresden.de.

Abstract

Over 10% of pheochromocytoma and paraganglioma (PPGL) patients have malignant disease at their first presentation in the clinic. Development of malignancy and the underlying molecular pathways in PPGLs are poorly understood and efficient treatment strategies are missing. Marine sponges provide a natural source of promising anti-tumorigenic and anti-metastatic agents. We evaluate the anti-tumorigenic and anti-metastatic potential of Aeroplysinin-1 and Isofistularin-3, two secondary metabolites isolated from the marine sponge Aplysina aerophoba, on pheochromocytoma cells. Aeroplysinin-1 diminished the number of proliferating cells and reduced spheroid growth significantly. Beside these anti-tumorigenic activity, Aeroplysinin-1 decreased the migration ability of the cells significantly (p = 0.01), whereas, the invasion capacity was not affected. Aeroplysinin-1 diminished the high adhesion capacity of the MTT cells to collagen (p < 0.001) and, furthermore, reduced the ability to form spheroids significantly. Western Blot and qRT-PCR analysis showed a downregulation of integrin β1 that might explain the lower adhesion and migration capacity after Aeroplysinin-1 treatment. Isofistularin-3 showed only a negligible influence on proliferative and pro-metastatic cell properties. These in vitro investigations show promise for the application of the sponge-derived marine drug, Aeroplysinin-1 as anti-tumorigenic and anti-metastatic agent against PPGLs for the first time.

KEYWORDS:

Aeroplysinin; Isofistularin; cancer progression; cell adhesion molecules; hypoxia; integrin β1; marine sponges; metastasis; pheochromocytoma and paraganglioma

PMID:
29783778
PMCID:
PMC5983303
DOI:
10.3390/md16050172
[Indexed for MEDLINE]
Free PMC Article

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