Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Riedl, S; Rinner, B; Schaider, H; Liegl-Atzwanger, B; Meditz, K; Preishuber-Pflügl, J; Grissenberger, S; Lohner, K; Zweytick, D.
In vitro and in vivo cytotoxic activity of human lactoferricin derived antitumor peptide R-DIM-P-LF11-334 on human malignant melanoma.
Oncotarget. 2017; 8(42):71817-71832
Doi: 10.18632/oncotarget.17823
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- Führende Autor*innen der Med Uni Graz
- Rinner Beate
- Co-Autor*innen der Med Uni Graz
- Liegl-Atzwanger Bernadette
- Meditz Katharina
- Schaider Helmut
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- Abstract:
- Di-peptides derived from the human host defense peptide lactoferricin were previously described to specifically interact with the negatively charged lipid phosphatidylserine exposed by cancer cells. In this study one further derivative, namely R-DIM-P-LF11-334 is shown to exhibit even increased cancer toxicity in vitro and in vivo while non-neoplastic cells are not harmed. In liposomal model systems composed of phosphatidylserine mimicking cancerous and phosphatidylcholine mimicking non-cancerous membranes the specific interaction with the cancer marker PS was confirmed by specific induction of membrane perturbation and permeabilization in presence of the peptide. In vitro studies with cell lines of human malignant melanoma, such as A375, or primary cells of human melanoma metastases to the brain, as MUG Mel1, and non-neoplastic human dermal fibroblasts NHDF revealed high cytotoxic effect of R-DIM-P-LF11-334 on melanoma cells of A375 and MUG Mel1, whereas only minor effect on the dermal fibroblasts NHDF was observed, yielding an about 20-fold killing-specificity for A375 and MUG-Mel1. The LC50 values for melanoma A375 and MUG Mel1 were about 10 μM. Analysis of secondary structure of the peptide revealed an increase in the proportion of β-sheets exclusively in presence of the cancer mimic. Stability studies further indicated a potential adequate stability in blood or under stringent conditions. Importantly the cytotoxic effect on cancer cells was also proven in vivo in mouse xenografts of human melanoma, where peptide treatment induced strong tumor regression and in average a tumor area reduction of 85% compared to tumors of control mice without peptide treatment.
- Find related publications in this database (Keywords)
- human melanoma
- antitumor peptide
- cancer treatment
- phosphatidylserine
- mouse xenograft