Design of human lactoferricin derived antitumor peptides-activity and specificity against malignant melanoma in 2D and 3D model studies

Biochimica Et Biophysica Acta. Biomembranes
Sarah GrissenbergerDagmar Zweytick

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. Furt...Continue Reading

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Sep 20, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yamil LiscanoJean Paul Delgado

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