Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Grissenberger, S; Riedl, S; Rinner, B; Leber, R; Zweytick, D.
Design of human lactoferricin derived antitumor peptides-activity and specificity against malignant melanoma in 2D and 3D model studies.
Biochim Biophys Acta Biomembr. 2020; 183264-183264.
Doi: 10.1016/j.bbamem.2020.183264
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- Führende Autor*innen der Med Uni Graz
- Leber Regina
- Co-Autor*innen der Med Uni Graz
- Riedl Sabrina
- Rinner Beate
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- Abstract:
- The aim of this study was to develop effective and specific anti-cancer drugs based on membrane active peptides. In previous studies we showed that human lactoferricin (hLFcin) derived peptides facilitate specific killing of cancer cells. These antitumor peptides were found by conventional melanoma two-dimensional (2D) cell cultures to induce apoptosis of cancer cells and to specifically target lipid phosphatidylserine located on the outside of cancer cell membranes. In order to have a more relevant in vitro model able to mimic the natural microenvironments of tumor tissues we established three-dimensional (3D) multicellular tumor spheroids (MCTS). We used a set of (retro) di-peptides derived from LF11, an 11 amino acid long fragment of hLFcin, which differed in peptide length, positive net charge and hydrophobicity and determined antitumor activity and non-specific toxicity on non-neoplastic cells using 2D and 3D model systems. 2D studies unveiled a correlation between length, positive net charge and hydrophobicity of peptides and their specific antitumor activity. (Retro) di-peptides as R-DIM-P-LF11-215 and DIM-LF11-322 with a net charge of +9 and moderate hydrophobicity exhibited the highest specific antitumor activity. Further evaluation of the peptides anticancer activity by 3D in vitro studies confirmed their higher activity and cancer specificity compared to their parent R-DIM-P-LF11, with the exception of DIM-LF11-339. This highly hydrophobic peptide caused cell death mainly at the border of tumor spheroids indicating that too high hydrophobicity may prevent peptides from reaching the center of the spheroids. Copyright © 2020. Published by Elsevier B.V.
- Find related publications in this database (Keywords)
- Antitumor peptides
- Lactoferricin
- Melanoma
- 2D and 3D in vitro studies