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Secondary Metabolites from the Culture of the Marine-derived Fungus Paradendryphiella salina PC 362H and Evaluation of the Anticancer Activity of Its Metabolite Hyalodendrin

High-throughput screening assays have been designed to identify compounds capable of inhibiting phenotypes involved in cancer aggressiveness. However, most studies used commercially available chemical libraries. This prompted us to explore natural products isolated from marine-derived fungi as a new...

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Autores principales: Dezaire, Ambre, Marchand, Christophe H., Vallet, Marine, Ferrand, Nathalie, Chaouch, Soraya, Mouray, Elisabeth, Larsen, Annette K., Sabbah, Michèle, Lemaire, Stéphane D., Prado, Soizic, Escargueil, Alexandre E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230232/
https://www.ncbi.nlm.nih.gov/pubmed/32260204
http://dx.doi.org/10.3390/md18040191
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author Dezaire, Ambre
Marchand, Christophe H.
Vallet, Marine
Ferrand, Nathalie
Chaouch, Soraya
Mouray, Elisabeth
Larsen, Annette K.
Sabbah, Michèle
Lemaire, Stéphane D.
Prado, Soizic
Escargueil, Alexandre E.
author_facet Dezaire, Ambre
Marchand, Christophe H.
Vallet, Marine
Ferrand, Nathalie
Chaouch, Soraya
Mouray, Elisabeth
Larsen, Annette K.
Sabbah, Michèle
Lemaire, Stéphane D.
Prado, Soizic
Escargueil, Alexandre E.
author_sort Dezaire, Ambre
collection PubMed
description High-throughput screening assays have been designed to identify compounds capable of inhibiting phenotypes involved in cancer aggressiveness. However, most studies used commercially available chemical libraries. This prompted us to explore natural products isolated from marine-derived fungi as a new source of molecules. In this study, we established a chemical library from 99 strains corresponding to 45 molecular operational taxonomic units and evaluated their anticancer activity against the MCF7 epithelial cancer cell line and its invasive stem cell-like MCF7-Sh-WISP2 counterpart. We identified the marine fungal Paradendryphiella salina PC 362H strain, isolated from the brown alga Pelvetia caniculata (PC), as one of the most promising fungi which produce active compounds. Further chemical and biological characterizations of the culture of the Paradendryphiella salina PC 362H strain identified (-)-hyalodendrin as the active secondary metabolite responsible for the cytotoxic activity of the crude extract. The antitumor activity of (-)-hyalodendrin was not only limited to the MCF7 cell lines, but also prominent on cancer cells with invasive phenotypes including colorectal cancer cells resistant to chemotherapy. Further investigations showed that treatment of MCF7-Sh-WISP2 cells with (-)-hyalodendrin induced changes in the phosphorylation status of p53 and altered expression of HSP60, HSP70 and PRAS40 proteins. Altogether, our study reveals that this uninvestigated marine fungal crude extract possesses a strong therapeutic potential against tumor cells with aggressive phenotypes and confirms that members of the epidithiodioxopiperazines are interesting fungal toxins with anticancer activities.
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spelling pubmed-72302322020-05-28 Secondary Metabolites from the Culture of the Marine-derived Fungus Paradendryphiella salina PC 362H and Evaluation of the Anticancer Activity of Its Metabolite Hyalodendrin Dezaire, Ambre Marchand, Christophe H. Vallet, Marine Ferrand, Nathalie Chaouch, Soraya Mouray, Elisabeth Larsen, Annette K. Sabbah, Michèle Lemaire, Stéphane D. Prado, Soizic Escargueil, Alexandre E. Mar Drugs Article High-throughput screening assays have been designed to identify compounds capable of inhibiting phenotypes involved in cancer aggressiveness. However, most studies used commercially available chemical libraries. This prompted us to explore natural products isolated from marine-derived fungi as a new source of molecules. In this study, we established a chemical library from 99 strains corresponding to 45 molecular operational taxonomic units and evaluated their anticancer activity against the MCF7 epithelial cancer cell line and its invasive stem cell-like MCF7-Sh-WISP2 counterpart. We identified the marine fungal Paradendryphiella salina PC 362H strain, isolated from the brown alga Pelvetia caniculata (PC), as one of the most promising fungi which produce active compounds. Further chemical and biological characterizations of the culture of the Paradendryphiella salina PC 362H strain identified (-)-hyalodendrin as the active secondary metabolite responsible for the cytotoxic activity of the crude extract. The antitumor activity of (-)-hyalodendrin was not only limited to the MCF7 cell lines, but also prominent on cancer cells with invasive phenotypes including colorectal cancer cells resistant to chemotherapy. Further investigations showed that treatment of MCF7-Sh-WISP2 cells with (-)-hyalodendrin induced changes in the phosphorylation status of p53 and altered expression of HSP60, HSP70 and PRAS40 proteins. Altogether, our study reveals that this uninvestigated marine fungal crude extract possesses a strong therapeutic potential against tumor cells with aggressive phenotypes and confirms that members of the epidithiodioxopiperazines are interesting fungal toxins with anticancer activities. MDPI 2020-04-03 /pmc/articles/PMC7230232/ /pubmed/32260204 http://dx.doi.org/10.3390/md18040191 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
Dezaire, Ambre
Marchand, Christophe H.
Vallet, Marine
Ferrand, Nathalie
Chaouch, Soraya
Mouray, Elisabeth
Larsen, Annette K.
Sabbah, Michèle
Lemaire, Stéphane D.
Prado, Soizic
Escargueil, Alexandre E.
Secondary Metabolites from the Culture of the Marine-derived Fungus Paradendryphiella salina PC 362H and Evaluation of the Anticancer Activity of Its Metabolite Hyalodendrin
title Secondary Metabolites from the Culture of the Marine-derived Fungus Paradendryphiella salina PC 362H and Evaluation of the Anticancer Activity of Its Metabolite Hyalodendrin
title_full Secondary Metabolites from the Culture of the Marine-derived Fungus Paradendryphiella salina PC 362H and Evaluation of the Anticancer Activity of Its Metabolite Hyalodendrin
title_fullStr Secondary Metabolites from the Culture of the Marine-derived Fungus Paradendryphiella salina PC 362H and Evaluation of the Anticancer Activity of Its Metabolite Hyalodendrin
title_full_unstemmed Secondary Metabolites from the Culture of the Marine-derived Fungus Paradendryphiella salina PC 362H and Evaluation of the Anticancer Activity of Its Metabolite Hyalodendrin
title_short Secondary Metabolites from the Culture of the Marine-derived Fungus Paradendryphiella salina PC 362H and Evaluation of the Anticancer Activity of Its Metabolite Hyalodendrin
title_sort secondary metabolites from the culture of the marine-derived fungus paradendryphiella salina pc 362h and evaluation of the anticancer activity of its metabolite hyalodendrin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230232/
https://www.ncbi.nlm.nih.gov/pubmed/32260204
http://dx.doi.org/10.3390/md18040191
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