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In Model, In Vitro and In Vivo Killing Efficacy of Antitumor Peptide RDP22 on MUG-Mel2, a Patient Derived Cell Line of an Aggressive Melanoma Metastasis

The host defense derived peptide was assessed in different model systems with increasing complexity employing the highly aggressive NRAS mutated melanoma metastases cell line MUG-Mel2. Amongst others, fluorescence microscopy and spectroscopy, as well as cell death studies were applied for liposomal,...

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Autores principales: Wußmann, Maximiliane, Groeber-Becker, Florian Kai, Riedl, Sabrina, Alihodzic, Dina, Padaric, Daniel, Gerlitz, Lisa, Stallinger, Alexander, Liegl-Atzwanger, Bernadette, Zweytick, Dagmar, Rinner, Beate
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687695/
https://www.ncbi.nlm.nih.gov/pubmed/36428530
http://dx.doi.org/10.3390/biomedicines10112961
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author Wußmann, Maximiliane
Groeber-Becker, Florian Kai
Riedl, Sabrina
Alihodzic, Dina
Padaric, Daniel
Gerlitz, Lisa
Stallinger, Alexander
Liegl-Atzwanger, Bernadette
Zweytick, Dagmar
Rinner, Beate
author_facet Wußmann, Maximiliane
Groeber-Becker, Florian Kai
Riedl, Sabrina
Alihodzic, Dina
Padaric, Daniel
Gerlitz, Lisa
Stallinger, Alexander
Liegl-Atzwanger, Bernadette
Zweytick, Dagmar
Rinner, Beate
author_sort Wußmann, Maximiliane
collection PubMed
description The host defense derived peptide was assessed in different model systems with increasing complexity employing the highly aggressive NRAS mutated melanoma metastases cell line MUG-Mel2. Amongst others, fluorescence microscopy and spectroscopy, as well as cell death studies were applied for liposomal, 2D and 3D in vitro models including tumor spheroids without or within skin models and in vivo mouse xenografts. Summarized, MUG-Mel2 cells were shown to significantly expose the negatively charged lipid phosphatidylserine on their plasma membranes, showing they are successfully targeted by RDP22. The peptide was able to induce cell death in MUG-Mel2 2D and 3D cultures, where it was able to kill tumor cells even inside the core of tumor spheroids or inside a melanoma organotypic model. In vitro studies indicated cell death by apoptosis upon peptide treatment with an LC(50) of 8.5 µM and seven-fold specificity for the melanoma cell line MUG-Mel2 over normal dermal fibroblasts. In vivo studies in mice xenografts revealed effective tumor regression upon intratumoral peptide injection, indicated by the strong clearance of pigmented tumor cells and tremendous reduction in tumor size and proliferation, which was determined histologically. The peptide RDP22 has clearly shown high potential against the melanoma cell line MUG-Mel2 in vitro and in vivo.
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spelling pubmed-96876952022-11-25 In Model, In Vitro and In Vivo Killing Efficacy of Antitumor Peptide RDP22 on MUG-Mel2, a Patient Derived Cell Line of an Aggressive Melanoma Metastasis Wußmann, Maximiliane Groeber-Becker, Florian Kai Riedl, Sabrina Alihodzic, Dina Padaric, Daniel Gerlitz, Lisa Stallinger, Alexander Liegl-Atzwanger, Bernadette Zweytick, Dagmar Rinner, Beate Biomedicines Article The host defense derived peptide was assessed in different model systems with increasing complexity employing the highly aggressive NRAS mutated melanoma metastases cell line MUG-Mel2. Amongst others, fluorescence microscopy and spectroscopy, as well as cell death studies were applied for liposomal, 2D and 3D in vitro models including tumor spheroids without or within skin models and in vivo mouse xenografts. Summarized, MUG-Mel2 cells were shown to significantly expose the negatively charged lipid phosphatidylserine on their plasma membranes, showing they are successfully targeted by RDP22. The peptide was able to induce cell death in MUG-Mel2 2D and 3D cultures, where it was able to kill tumor cells even inside the core of tumor spheroids or inside a melanoma organotypic model. In vitro studies indicated cell death by apoptosis upon peptide treatment with an LC(50) of 8.5 µM and seven-fold specificity for the melanoma cell line MUG-Mel2 over normal dermal fibroblasts. In vivo studies in mice xenografts revealed effective tumor regression upon intratumoral peptide injection, indicated by the strong clearance of pigmented tumor cells and tremendous reduction in tumor size and proliferation, which was determined histologically. The peptide RDP22 has clearly shown high potential against the melanoma cell line MUG-Mel2 in vitro and in vivo. MDPI 2022-11-17 /pmc/articles/PMC9687695/ /pubmed/36428530 http://dx.doi.org/10.3390/biomedicines10112961 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wußmann, Maximiliane
Groeber-Becker, Florian Kai
Riedl, Sabrina
Alihodzic, Dina
Padaric, Daniel
Gerlitz, Lisa
Stallinger, Alexander
Liegl-Atzwanger, Bernadette
Zweytick, Dagmar
Rinner, Beate
In Model, In Vitro and In Vivo Killing Efficacy of Antitumor Peptide RDP22 on MUG-Mel2, a Patient Derived Cell Line of an Aggressive Melanoma Metastasis
title In Model, In Vitro and In Vivo Killing Efficacy of Antitumor Peptide RDP22 on MUG-Mel2, a Patient Derived Cell Line of an Aggressive Melanoma Metastasis
title_full In Model, In Vitro and In Vivo Killing Efficacy of Antitumor Peptide RDP22 on MUG-Mel2, a Patient Derived Cell Line of an Aggressive Melanoma Metastasis
title_fullStr In Model, In Vitro and In Vivo Killing Efficacy of Antitumor Peptide RDP22 on MUG-Mel2, a Patient Derived Cell Line of an Aggressive Melanoma Metastasis
title_full_unstemmed In Model, In Vitro and In Vivo Killing Efficacy of Antitumor Peptide RDP22 on MUG-Mel2, a Patient Derived Cell Line of an Aggressive Melanoma Metastasis
title_short In Model, In Vitro and In Vivo Killing Efficacy of Antitumor Peptide RDP22 on MUG-Mel2, a Patient Derived Cell Line of an Aggressive Melanoma Metastasis
title_sort in model, in vitro and in vivo killing efficacy of antitumor peptide rdp22 on mug-mel2, a patient derived cell line of an aggressive melanoma metastasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687695/
https://www.ncbi.nlm.nih.gov/pubmed/36428530
http://dx.doi.org/10.3390/biomedicines10112961
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