TY  - JOUR
A1  - Wußmann, Maximiliane
A1  - Groeber-Becker, Florian Kai
A1  - Riedl, Sabrina
A1  - Alihodzic, Dina
A1  - Padaric, Daniel
A1  - Gerlitz, Lisa
A1  - Stallinger, Alexander
A1  - Liegl-Atzwanger, Bernadette
A1  - Zweytick, Dagmar
A1  - Rinner, Beate
T1  - 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
JF  - Biomedicines
N2  - 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.
KW  - melanoma metastases
KW  - NRAS mutation
KW  - antitumor peptide
KW  - tumor model systems
KW  - phosphatidylserine
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297525
SN  - 2227-9059
VL  - 10
IS  - 11
ER  -