Abstract
LF11-322 (PFWRIRIRR-NH2) (PFR peptide), a nine amino acid-residue peptide fragment derived from human lactoferricin, possesses potent cytotoxicity against bacteria. We report here the discovery and characterization of its antitumor activity in leukemia cells. PFR peptide inhibited the proliferation of MEL and HL-60 leukemia cells by inducing cell death in the absence of the classical features of apoptosis, including chromatin condensation, Annexin V staining, Caspase activation and increase of abundance of pro-apoptotic proteins. Instead, necrotic cell death as evidenced by increasing intracellular PI staining and LDH release, inducing membrane disruption and up-regulating intracellular calcium level, was observed following PFR peptide treatment. In addition to necrotic cell death, PFR peptide also induced G0/G1 cell cycle arrest. Moreover, PFR peptide exhibited favorable antitumor activity and tolerability in vivo. These findings thus provide a new clue of antimicrobial peptides as a potential novel therapy for leukemia.
Highlights
Antimicrobial peptides (AMPs) are cationic molecules generated in the biological defense system as a first line of defense against invading pathogenic microorganisms[1,2]
Cell viability in the presence of PFR peptide was assessed by MTT assay in three types of leukemia cell lines, including murine erythroleukemia MEL cells, human promyelocytic leukemia HL-60 cells and human immortalized myelogenous leukemia K562 cells
These results suggested that PFR peptide inhibited cell proliferation in certain types of leukemia cells
Summary
Antimicrobial peptides (AMPs) are cationic molecules generated in the biological defense system as a first line of defense against invading pathogenic microorganisms[1,2]. In addition to the antimicrobial activity, a growing number of studies have reported their anticancer activity[9,10] Among those AMPs, Lactoferrin (LF) is a mammalian cationic iron-binding glycoprotein with a molecular weight of ∼ 80 kDa. LF is widely distributed in biological fluids and expressed by the immune cells upon pathogen stimulation[11,12,13,14]. LF11, an 11 amino acid residue peptide fragment corresponding to hLFcin 21–31(FQWQRNIRKVR-NH2), has weak antibacterial activity[27,28,29], and approximately 150 LF11 mutants were designed to optimize its biological activity. We investigated and characterized anti-tumor activity of PFR peptide in leukemia cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
