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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

Affiliation
Translational Center Regenerative Therapies TLC-RT, Fraunhofer Institute for Silicate Research ISC, Neunerplatz 2, 97080 Würzburg, Germany
Wußmann, Maximiliane;
Affiliation
Translational Center Regenerative Therapies TLC-RT, Fraunhofer Institute for Silicate Research ISC, Neunerplatz 2, 97080 Würzburg, Germany
Groeber-Becker, Florian Kai;
ORCID
0000-0002-2608-0753
Affiliation
Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/III, A-8010 Graz, Austria
Riedl, Sabrina;
Affiliation
Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/III, A-8010 Graz, Austria
Alihodzic, Dina;
Affiliation
Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/III, A-8010 Graz, Austria
Padaric, Daniel;
Affiliation
Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/III, A-8010 Graz, Austria
Gerlitz, Lisa;
Affiliation
Division of Biomedical Research, Medical University of Graz, Stiftingtalstrasse 24, A-8010 Graz, Austria
Stallinger, Alexander;
ORCID
0000-0003-2229-5535
Affiliation
Diagnostic and Research Institute of Pathology, Medical University of Graz, Neue Stiftingtalstrasse 6, A-8010 Graz, Austria
Liegl-Atzwanger, Bernadette;
ORCID
0000-0002-4766-7713
Affiliation
Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/III, A-8010 Graz, Austria
Zweytick, Dagmar;
Affiliation
BioTechMed-Graz, Mozartgasse 12/II, A-8010 Graz, Austria
Rinner, Beate

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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