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Anti-Tumor Activity vs. Normal Cell Toxicity: Therapeutic Potential of the Bromotyrosines Aerothionin and Homoaerothionin In Vitro

Novel strategies to treat cancer effectively without adverse effects on the surrounding normal tissue are urgently needed. Marine sponges provide a natural and renewable source of promising anti-tumor agents. Here, we investigated the anti-tumor activity of Aerothionin and Homoaerothionin, two bromo...

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Autores principales: Drechsel, Antje, Helm, Jana, Ehrlich, Hermann, Pantovic, Snezana, Bornstein, Stefan R., Bechmann, Nicole
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281235/
https://www.ncbi.nlm.nih.gov/pubmed/32369901
http://dx.doi.org/10.3390/md18050236
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author Drechsel, Antje
Helm, Jana
Ehrlich, Hermann
Pantovic, Snezana
Bornstein, Stefan R.
Bechmann, Nicole
author_facet Drechsel, Antje
Helm, Jana
Ehrlich, Hermann
Pantovic, Snezana
Bornstein, Stefan R.
Bechmann, Nicole
author_sort Drechsel, Antje
collection PubMed
description Novel strategies to treat cancer effectively without adverse effects on the surrounding normal tissue are urgently needed. Marine sponges provide a natural and renewable source of promising anti-tumor agents. Here, we investigated the anti-tumor activity of Aerothionin and Homoaerothionin, two bromotyrosines isolated from the marine demosponge Aplysina cavernicola, on two mouse pheochromocytoma cells, MPC and MTT. To determine the therapeutic window of these metabolites, we furthermore explored their cytotoxicity on cells of the normal tissue. Both metabolites diminished the viability of the pheochromocytoma cell lines significantly from a concentration of 25 µM under normoxic and hypoxic conditions. Treatment of MPC cells leads moreover to a reduction in the number of proliferating cells. To confirm the anti-tumor activity of these bromotyrosines, 3D-pheochromocytoma cell spheroids were treated with 10 µM of either Aerothionin or Homoaerothionin, resulting in a significant reduction or even complete inhibition of the spheroid growth. Both metabolites reduced viability of normal endothelial cells to a comparable extent at higher micromolar concentration, while the viability of fibroblasts was increased. Our in vitro results show promise for the application of Aerothionin and Homoaerothionin as anti-tumor agents against pheochromocytomas and suggest acceptable toxicity on normal tissue cells.
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spelling pubmed-72812352020-06-15 Anti-Tumor Activity vs. Normal Cell Toxicity: Therapeutic Potential of the Bromotyrosines Aerothionin and Homoaerothionin In Vitro Drechsel, Antje Helm, Jana Ehrlich, Hermann Pantovic, Snezana Bornstein, Stefan R. Bechmann, Nicole Mar Drugs Article Novel strategies to treat cancer effectively without adverse effects on the surrounding normal tissue are urgently needed. Marine sponges provide a natural and renewable source of promising anti-tumor agents. Here, we investigated the anti-tumor activity of Aerothionin and Homoaerothionin, two bromotyrosines isolated from the marine demosponge Aplysina cavernicola, on two mouse pheochromocytoma cells, MPC and MTT. To determine the therapeutic window of these metabolites, we furthermore explored their cytotoxicity on cells of the normal tissue. Both metabolites diminished the viability of the pheochromocytoma cell lines significantly from a concentration of 25 µM under normoxic and hypoxic conditions. Treatment of MPC cells leads moreover to a reduction in the number of proliferating cells. To confirm the anti-tumor activity of these bromotyrosines, 3D-pheochromocytoma cell spheroids were treated with 10 µM of either Aerothionin or Homoaerothionin, resulting in a significant reduction or even complete inhibition of the spheroid growth. Both metabolites reduced viability of normal endothelial cells to a comparable extent at higher micromolar concentration, while the viability of fibroblasts was increased. Our in vitro results show promise for the application of Aerothionin and Homoaerothionin as anti-tumor agents against pheochromocytomas and suggest acceptable toxicity on normal tissue cells. MDPI 2020-05-01 /pmc/articles/PMC7281235/ /pubmed/32369901 http://dx.doi.org/10.3390/md18050236 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Drechsel, Antje
Helm, Jana
Ehrlich, Hermann
Pantovic, Snezana
Bornstein, Stefan R.
Bechmann, Nicole
Anti-Tumor Activity vs. Normal Cell Toxicity: Therapeutic Potential of the Bromotyrosines Aerothionin and Homoaerothionin In Vitro
title Anti-Tumor Activity vs. Normal Cell Toxicity: Therapeutic Potential of the Bromotyrosines Aerothionin and Homoaerothionin In Vitro
title_full Anti-Tumor Activity vs. Normal Cell Toxicity: Therapeutic Potential of the Bromotyrosines Aerothionin and Homoaerothionin In Vitro
title_fullStr Anti-Tumor Activity vs. Normal Cell Toxicity: Therapeutic Potential of the Bromotyrosines Aerothionin and Homoaerothionin In Vitro
title_full_unstemmed Anti-Tumor Activity vs. Normal Cell Toxicity: Therapeutic Potential of the Bromotyrosines Aerothionin and Homoaerothionin In Vitro
title_short Anti-Tumor Activity vs. Normal Cell Toxicity: Therapeutic Potential of the Bromotyrosines Aerothionin and Homoaerothionin In Vitro
title_sort anti-tumor activity vs. normal cell toxicity: therapeutic potential of the bromotyrosines aerothionin and homoaerothionin in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281235/
https://www.ncbi.nlm.nih.gov/pubmed/32369901
http://dx.doi.org/10.3390/md18050236
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