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Mar. Drugs 2018, 16(5), 172; https://doi.org/10.3390/md16050172

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

1
Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, 01307 Dresden, Germany
2
Institute of Experimental Physics, TU Bergakademie Freiberg, Leipziger 23, 09599 Freiberg, Germany
3
Department of Medicine III, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, 01307 Dresden, Germany
4
BromMarin GmbH, Wernerstraße 1, 09599 Freiberg, Germany
5
Center for Regenerative Therapies Dresden, Technical University Dresden, Fetscherstrasse 105, 01307 Dresden, Germany
*
Author to whom correspondence should be addressed.
Received: 24 April 2018 / Revised: 12 May 2018 / Accepted: 15 May 2018 / Published: 20 May 2018
(This article belongs to the Collection Marine Compounds and Cancer)
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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. View Full-Text
Keywords: marine sponges; Aeroplysinin; Isofistularin; pheochromocytoma and paraganglioma; metastasis; cancer progression; cell adhesion molecules; integrin β1; hypoxia marine sponges; Aeroplysinin; Isofistularin; pheochromocytoma and paraganglioma; metastasis; cancer progression; cell adhesion molecules; integrin β1; hypoxia
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Bechmann, N.; Ehrlich, H.; Eisenhofer, G.; Ehrlich, A.; Meschke, S.; Ziegler, C.G.; Bornstein, S.R. Anti-Tumorigenic and Anti-Metastatic Activity of the Sponge-Derived Marine Drugs Aeroplysinin-1 and Isofistularin-3 against Pheochromocytoma In Vitro. Mar. Drugs 2018, 16, 172.

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