PFR peptide, one of the antimicrobial peptides identified from the derivatives of lactoferrin, induces necrosis in leukemia cells

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.

Cryptides: latent peptides everywhere

“…Some examples are represented by the fragment 1-11 deriving from the reduction of lactoferricin H (GRRRSVQWCAV) with antiviral and high antibacterial activity (Bruni et al 2016;Wang et al 2016), which were confirmed in animal models and in a phase 1 study in human volunteers (Bruni et al 2016), and by a tetrameric peptide derived from lactoferricin B ((RRWQWR) 4 ) exhibiting specific cytotoxic effects against oral squamous-cell carcinoma cell lines (Solarte et al 2015). This antitumor activity was further confirmed by the PFR-peptide (Table 3) derived from lactoferricin H that induced necrotic cell death and G0/G1 cell cycle arrest in MEL and HL-60 leukemia cell lines (Lu et al 2016). In this study, researchers demonstrated that PFR-peptide inhibited leukemia cell growth in vivo in immune-compromised mice transplanted with MEL cells.…”

miR-663a regulates growth of colon cancer cells, after administration of antimicrobial peptides, by targeting CXCR4-p21 pathway

“…From previous reports, the mechanism of the anti-cancer effects of AMPs against cancer cells includes multiple directions such as apoptosis, necrosis, and autophagy [35–37]. We previously reported that FF/CAP18 induces apoptotic cell death in HCT116 cells through dynamic changes in the levels of metabolic profiles and revealed that the glycolytic pathway was restricted, resulting in reduced energy status [38].…”

Synthesis of breast cancer targeting conjugate of temporin-SHa analog and its effect on pro- and anti-apoptotic protein expression in MCF-7 cells

“…Although AMPs are primarily known for their antimicrobial properties, some examples and their derivatives are reported as potent antitumor agents with low toxicity such as temporin-1CEa, ascaphin-8, alyteserin-2 and magainin-2 [13][14][15][16][17]. These AMPs bind to the plasma membrane and cause cell death by either necrosis or apoptosis [18][19][20][21].…”