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The marine natural product mimic MPM-1 is cytolytic and induces DAMP release from human cancer cell lines

Bioprospecting contributes to the discovery of new molecules with anticancer properties. Compounds with cytolytic activity and the ability to induce immunogenic cell death can be administered as intratumoral injections with the aim to activate anti-tumor immune responses by causing the release of tu...

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Autores principales: von Hofsten, Susannah, Paulsen, Marianne Hagensen, Magnussen, Synnøve Norvoll, Ausbacher, Dominik, Kranz, Mathias, Bayer, Annette, Strøm, Morten B., Berge, Gerd
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9481558/
https://www.ncbi.nlm.nih.gov/pubmed/36114339
http://dx.doi.org/10.1038/s41598-022-19597-4
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author von Hofsten, Susannah
Paulsen, Marianne Hagensen
Magnussen, Synnøve Norvoll
Ausbacher, Dominik
Kranz, Mathias
Bayer, Annette
Strøm, Morten B.
Berge, Gerd
author_facet von Hofsten, Susannah
Paulsen, Marianne Hagensen
Magnussen, Synnøve Norvoll
Ausbacher, Dominik
Kranz, Mathias
Bayer, Annette
Strøm, Morten B.
Berge, Gerd
author_sort von Hofsten, Susannah
collection PubMed
description Bioprospecting contributes to the discovery of new molecules with anticancer properties. Compounds with cytolytic activity and the ability to induce immunogenic cell death can be administered as intratumoral injections with the aim to activate anti-tumor immune responses by causing the release of tumor antigens as well as damage-associated molecular patterns (DAMPs) from dying cancer cells. In the present study, we report the cytolytic and DAMP-releasing effects of a new natural product mimic termed MPM-1 that was inspired by the marine Eusynstyelamides. We found that MPM-1 rapidly killed cancer cells in vitro by inducing a necrosis-like death, which was accompanied by lysosomal swelling and perturbation of autophagy in HSC-3 (human oral squamous cell carcinoma) cells. MPM-1 also induced release of the DAMPs adenosine triphosphate (ATP) and high mobility group box 1 (HMGB1) from Ramos (B-cell lymphoma) and HSC-3 cells, as well as cell surface expression of calreticulin in HSC-3 cells. This indicates that MPM-1 has the ability to induce immunogenic cell death, further suggesting that it may have potential as a novel anticancer compound.
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spelling pubmed-94815582022-09-18 The marine natural product mimic MPM-1 is cytolytic and induces DAMP release from human cancer cell lines von Hofsten, Susannah Paulsen, Marianne Hagensen Magnussen, Synnøve Norvoll Ausbacher, Dominik Kranz, Mathias Bayer, Annette Strøm, Morten B. Berge, Gerd Sci Rep Article Bioprospecting contributes to the discovery of new molecules with anticancer properties. Compounds with cytolytic activity and the ability to induce immunogenic cell death can be administered as intratumoral injections with the aim to activate anti-tumor immune responses by causing the release of tumor antigens as well as damage-associated molecular patterns (DAMPs) from dying cancer cells. In the present study, we report the cytolytic and DAMP-releasing effects of a new natural product mimic termed MPM-1 that was inspired by the marine Eusynstyelamides. We found that MPM-1 rapidly killed cancer cells in vitro by inducing a necrosis-like death, which was accompanied by lysosomal swelling and perturbation of autophagy in HSC-3 (human oral squamous cell carcinoma) cells. MPM-1 also induced release of the DAMPs adenosine triphosphate (ATP) and high mobility group box 1 (HMGB1) from Ramos (B-cell lymphoma) and HSC-3 cells, as well as cell surface expression of calreticulin in HSC-3 cells. This indicates that MPM-1 has the ability to induce immunogenic cell death, further suggesting that it may have potential as a novel anticancer compound. Nature Publishing Group UK 2022-09-16 /pmc/articles/PMC9481558/ /pubmed/36114339 http://dx.doi.org/10.1038/s41598-022-19597-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
von Hofsten, Susannah
Paulsen, Marianne Hagensen
Magnussen, Synnøve Norvoll
Ausbacher, Dominik
Kranz, Mathias
Bayer, Annette
Strøm, Morten B.
Berge, Gerd
The marine natural product mimic MPM-1 is cytolytic and induces DAMP release from human cancer cell lines
title The marine natural product mimic MPM-1 is cytolytic and induces DAMP release from human cancer cell lines
title_full The marine natural product mimic MPM-1 is cytolytic and induces DAMP release from human cancer cell lines
title_fullStr The marine natural product mimic MPM-1 is cytolytic and induces DAMP release from human cancer cell lines
title_full_unstemmed The marine natural product mimic MPM-1 is cytolytic and induces DAMP release from human cancer cell lines
title_short The marine natural product mimic MPM-1 is cytolytic and induces DAMP release from human cancer cell lines
title_sort marine natural product mimic mpm-1 is cytolytic and induces damp release from human cancer cell lines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9481558/
https://www.ncbi.nlm.nih.gov/pubmed/36114339
http://dx.doi.org/10.1038/s41598-022-19597-4
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