The NK‐lysin derived peptide NK‐2 preferentially kills cancer cells with increased surface levels of negatively charged phosphatidylserine

Abstract

The NK-lysin derived peptide NK-2 is a potent antibacterial, but non-toxic to a human keratinocyte cell line and of low hemolytic activity. Its target selectivity is based upon a strong binding preference to membranes containing anionic phospholipids, which are normally not found on the surface of human cells. Here, we analyzed the interaction of NK-2 with normal human lymphocytes and seven different human cancer cell lines and demonstrate that some of these cells expose negatively charged surface phosphatidylserine (PS), which presumably facilitates killing of the cells by NK-2. This is underlined by the specific intercalation of the peptide into PS-containing liposomes analyzed by fluorescence-resonance energy transfer spectroscopy.

The phospholipid code: a key component of dying cell recognition, tumor progression and host–microbe interactions

“…For example, NK-2, a synthetic cationic peptide derived from the porcine antimicrobial peptide NK-lysin, was tested on a range of human tumor cell lines and displayed significantly greater cytotoxic activity towards cell types that were exposing elevated levels of outer membrane PS. 54 Similarly, treatment of a range of mammalian tumor cell lines with four enantiomeric 9-mer CAPs derived from beetle defensins revealed a strong positive correlation between the sensitivity of cell types to CAP-mediated cytotoxicity and PS exposure. 55 Modification of the intracellular phospholipid code.…”

Interaction of an Antimicrobial Peptide with Membranes: Experiments and Simulations with NKCS

“…3,[7][8][9][10] The selectivity of the cytolytic mechanism is assumed to stem from inherent differences in the lipid composition of the target cells. 10 The NK-2 peptide, corresponding to residues 39-65 of the NK-lysin protein, has been investigated extensively due to its high antimicrobial [11][12][13] and anticancer qualities 14 as well as low hemolytic activity. 11 The peptide was found to reduce the transition temperature of the lipid bilayer in a concentration dependent manner by up to 10°C.…”

Specific Interaction between Ca2+ and Anionic Lipids in Cancer Cells along with Apoptosis

“…19) After the pre-incubation of tumor cells (2.0ϫ10 4 viable cells/ml) in a humidified atmosphere of 5% CO 2 at 37°C for 96 h, the tumor cells were processed for an Annexin-V-FLUOS Staining Kit (Roche Diagnostics, Switzerland) according to the manufacturer's instruction. The stained cells were analyzed using a flow cytometer with a single excitation 488 nm of 15 mW air-cooling Ar laser.…”