2. Academic Validation
  3. Selective anticancer activity of synthetic peptides derived from the host defence peptide tritrpticin

Selective anticancer activity of synthetic peptides derived from the host defence peptide tritrpticin

  • Biochim Biophys Acta Biomembr. 2020 Aug 1;1862(8):183228. doi: 10.1016/j.bbamem.2020.183228.
Mauricio Arias 1,  Evan F Haney 2,  Ashley L Hilchie 3,  Jennifer A Corcoran 4,  M Eric Hyndman 5,  Robert E W Hancock 2,  Hans J Vogel 6
Affiliations

Affiliations

  • 1 Biochemistry Research Group, Department of Biological Sciences, University of Calgary, 2500 University Dr. NW, Calgary, AB T2N 1N4, Canada; Biophysics Group, School of Physics, Faculty of Sciences, Universidad Nacional de Colombia - Sede Medellín, Calle 65 No 59A-110, Medellín, Colombia.
  • 2 Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
  • 3 Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 4R2, Canada; Department of Biology, Acadia University, Wolfville, NS B4P 2R6, Canada.
  • 4 Department of Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 4R2, Canada; Microbiology, Immunology and Infectious Disease Department, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada.
  • 5 Department of Surgery, Division of Urology, Southern Alberta Institute of Urology, University of Calgary, Calgary, AB T2V 1P9, Canada.
  • 6 Biochemistry Research Group, Department of Biological Sciences, University of Calgary, 2500 University Dr. NW, Calgary, AB T2N 1N4, Canada. Electronic address: [email protected].
PMID: 32126228 DOI: 10.1016/j.bbamem.2020.183228
Abstract

Antimicrobial peptides (AMPs) constitute a diverse family of peptides with the ability to protect their host against microbial infections. In addition to their ability to kill Microorganisms, several AMPs also exhibit selective cytotoxicity towards Cancer cells and are collectively referred to as Anticancer peptides (ACPs). Here a large library of AMPs, mainly derived from the porcine cathelicidin peptide, tritrpticin (VRRFPWWWPFLRR), were assessed for their Anticancer activity against the Jurkat T cell leukemia line. These Anticancer potencies were compared to the cytotoxicity of the peptides towards normal cells isolated from healthy donors, namely peripheral blood mononuclear cells (PBMCs) and red blood cells (RBCs; where hemolytic activity was assessed). Among the active tritrpticin derivatives, substitution of Arg by Lys enhanced the selectivity of the peptides towards Jurkat cells when compared to PBMCs. Additionally, the side chain length of the Lys residues was also optimized to further enhance the tritrpticin ACP selectivity at low concentrations. The mechanism of action of the peptides with high selectivity involved the permeabilization of the cytoplasmic membrane of Jurkat cells, without formation of apoptotic bodies. The incorporation of non-natural Lys-based cationic Amino acids could provide a new strategy to improve the selectivity of Other synthetic ACPs to enhance their potential for therapeutic use against leukemia cells.

Keywords

Anticancer peptides; Antimicrobial peptides; Host defence peptides; Jurkat cells; Selectivity; Tritrpticin.

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