Killing of melanoma cells and their metastases by human lactoferricin derivatives requires interaction with the cancer marker phosphatidylserine

Riedl, Sabrina, Rinner, Beate, Schaider, Helmut, Lohner, Karl and Zweytick, Dagmar (2014) Killing of melanoma cells and their metastases by human lactoferricin derivatives requires interaction with the cancer marker phosphatidylserine. BioMetals, 27 5: 981-997. doi:10.1007/s10534-014-9749-0


Author Riedl, Sabrina
Rinner, Beate
Schaider, Helmut
Lohner, Karl
Zweytick, Dagmar
Title Killing of melanoma cells and their metastases by human lactoferricin derivatives requires interaction with the cancer marker phosphatidylserine
Journal name BioMetals   Check publisher's open access policy
ISSN 0966-0844
1572-8773
Publication date 2014-10
Year available 2014
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1007/s10534-014-9749-0
Open Access Status
Volume 27
Issue 5
Start page 981
End page 997
Total pages 17
Place of publication Dordrecht, Netherlands
Publisher Springer Netherlands
Collection year 2015
Language eng
Formatted abstract
Despite favorable advancements in therapy cancer is still not curative in many cases, which is often due to inadequate specificity for tumor cells. In this study derivatives of a short cationic peptide derived from the human host defense peptide lactoferricin were optimized in their selective toxicity towards cancer cells. We proved that the target of these peptides is the negatively charged membrane lipid phosphatidylserine (PS), specifically exposed on the surface of cancer cells. We have studied the membrane interaction of three peptides namely LF11-322, its N-acyl derivative 6-methyloctanoyl-LF11-322 and its retro repeat derivative R(etro)-DIM-P-LF11-322 with liposomes mimicking cancerous and non-cancerous cell membranes composed of PS and phosphatidylcholine (PC), respectively. Calorimetric and permeability studies showed that N-acylation and even more the repeat derivative of LF11-322 leads to strongly improved interaction with the cancer mimic PS, whereas only the N-acyl derivative also slightly affects PC. Tryptophan fluorescence of selective peptide R-DIM-P-LF11-322 revealed specific peptide penetration into the PS membrane interface and circular dichroism showed change of its secondary structure by increase of proportion of β-sheets just in the presence of the cancer mimic. Data correlated with in vitro studies with cell lines of human melanomas, their metastases and melanocytes, revealing R-DIM-P-LF11-322 to exhibit strongly increased specificity for cancer cells. This indicates the need of high affinity to the target PS, a minimum length and net positive charge, an adequate but moderate hydrophobicity, and capability of adoption of a defined structure exclusively in presence of the target membrane for high antitumor activity.
Keyword Peptides
Cancer therapy
Liposomes
Melanoma
Membrane biophysics
Lactoferricin derivatives
Cell membrane permeabilization
Phosphatidylserine
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Official 2015 Collection
School of Medicine Publications
 
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