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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MDPI AG
2022-11-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/11/2961 |
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| author | Maximiliane Wußmann Florian Kai Groeber-Becker Sabrina Riedl Dina Alihodzic Daniel Padaric Lisa Gerlitz Alexander Stallinger Bernadette Liegl-Atzwanger Dagmar Zweytick Beate Rinner |
| author_facet | Maximiliane Wußmann Florian Kai Groeber-Becker Sabrina Riedl Dina Alihodzic Daniel Padaric Lisa Gerlitz Alexander Stallinger Bernadette Liegl-Atzwanger Dagmar Zweytick Beate Rinner |
| author_sort | Maximiliane Wußmann |
| collection | DOAJ |
| 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<sub>50</sub> 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. |
| first_indexed | 2024-03-09T18:27:07Z |
| format | Article |
| id | doaj.art-2b6266e9095f4b44af0b6f234964aec9 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T18:27:07Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-2b6266e9095f4b44af0b6f234964aec92023-11-24T07:46:52ZengMDPI AGBiomedicines2227-90592022-11-011011296110.3390/biomedicines10112961In Model, In Vitro and In Vivo Killing Efficacy of Antitumor Peptide RDP22 on MUG-Mel2, a Patient Derived Cell Line of an Aggressive Melanoma MetastasisMaximiliane Wußmann0Florian Kai Groeber-Becker1Sabrina Riedl2Dina Alihodzic3Daniel Padaric4Lisa Gerlitz5Alexander Stallinger6Bernadette Liegl-Atzwanger7Dagmar Zweytick8Beate Rinner9Translational Center Regenerative Therapies TLC-RT, Fraunhofer Institute for Silicate Research ISC, Neunerplatz 2, 97080 Würzburg, GermanyTranslational Center Regenerative Therapies TLC-RT, Fraunhofer Institute for Silicate Research ISC, Neunerplatz 2, 97080 Würzburg, GermanyInstitute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/III, A-8010 Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/III, A-8010 Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/III, A-8010 Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/III, A-8010 Graz, AustriaDivision of Biomedical Research, Medical University of Graz, Stiftingtalstrasse 24, A-8010 Graz, AustriaDiagnostic and Research Institute of Pathology, Medical University of Graz, Neue Stiftingtalstrasse 6, A-8010 Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/III, A-8010 Graz, AustriaBioTechMed-Graz, Mozartgasse 12/II, A-8010 Graz, AustriaThe 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<sub>50</sub> 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.https://www.mdpi.com/2227-9059/10/11/2961melanoma metastasesNRAS mutationantitumor peptidetumor model systemsphosphatidylserine |
| spellingShingle | Maximiliane Wußmann Florian Kai Groeber-Becker Sabrina Riedl Dina Alihodzic Daniel Padaric Lisa Gerlitz Alexander Stallinger Bernadette Liegl-Atzwanger Dagmar Zweytick Beate Rinner 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 Biomedicines melanoma metastases NRAS mutation antitumor peptide tumor model systems phosphatidylserine |
| 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 | melanoma metastases NRAS mutation antitumor peptide tumor model systems phosphatidylserine |
| url | https://www.mdpi.com/2227-9059/10/11/2961 |
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