Comparison of patient-derived high and low phosphatidylserine-exposing colorectal carcinoma cells in their interaction with anti-cancer peptides

Abstract

Current cancer treatment is frequently compromised by severe adverse effects on healthy cells and tissues as well as by the increasing burden of (multi-)drug resistances. Some representatives of small, amphipathic peptides known as host defense peptides possess the potential to overcome these limitations and to evolve as future anti-cancer therapeutics. Peptide NK-2, derived from porcine NK-lysin, was originally discovered due to its broad-spectrum antimicrobial activities. Today, also potent anti-cancer activity is proven and accompanied by low toxicity towards normal human cells. The molecular basis underlying this target selectivity remains rather elusive. Nevertheless, it is presumptive that preferential peptide interactions with surface factors non-abundant on healthy human cells play a key role. Here, we investigated the cytotoxicity of peptide NK-2 and structurally improved anti-cancer variants thereof against two patient-derived colorectal cancer cell lines, exposing high and low levels of phosphatidylserine on their cell surfaces, respectively. Concluding from a range of in vitro tests involving cellular as well as lipid vesicle-based methods, it is proposed that the magnitude of the accessible membrane surface charge is not a primarily decisive factor for selective peptide interactions. Instead, it is suggested that the level of membrane surface-exposed phosphatidylserine is of crucial importance for the activity of peptide NK-2 and enhanced variants thereof in terms of their cancer cell selectivity, the overall efficacy, as well as the underlying mode of action and kinetics. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Phospholipid Scramblases: Role in Cancer Progression and Anticancer Therapeutics

“…Human A375 melanoma cells that express 50-fold more PS than noncancerous HaCaT cells binds to the A375 melanoma cells with higher affinity for the membranolytic peptide temporin-1CEa ( Wang et al, 2016 ). Similarly, the membranolytic peptide NK2 exhibits preferential interaction with colorectal cancer cell lines ( Wilms and Andrä, 2017 ). Matrix metalloproteinase 2 (MMP2)-sensitive PS-modified nanoparticles were developed to target Tumor-associated macrophages (TAMs) in the tumor microenvironments.…”

Electrostatically Driven Encapsulation of Hydrophilic, Non-Conformational Peptide Epitopes into Liposomes

“…Circular dichroism (CD) spectroscopic studies, as well as zeta-potential and particle size measurements, were employed to study peptide-membrane interactions as a function of various physico-chemical properties, membrane compositions and peptide sequences [29,30,31]. Binding studies and encapsulation experiments using the two most commonly employed methods for the lab-scale preparation of peptide-loaded liposomes (i.e., thin-film hydration and microfluidic mixing), were then used to test whether the extent of electrostatic binding translates to corresponding levels of encapsulation.…”

Correlation of Antioxidant and Antiproliferative Activity of Amla and Ginger

“…Many studies showed its beneficial effect in lung, ovarian, colorectal, and gastric cancer [6][7][8]. In addition, dietary supplements containing ascorbic acid, lysine, proline, and green tea extracts are known to reduce the tumor growth in vivo studies [9][10][11][12]. Micromolar concentration of extracellular Vitamin C kills cancer cells but not normal cells in an H 2 O 2 -dependent manner [13].…”