A Tetrameric Peptide Derived from Bovine Lactoferricin Exhibits Specific Cytotoxic Effects against Oral Squamous-Cell Carcinoma Cell Lines

Abstract

Several short linear peptides derived from cyclic bovine lactoferricin were synthesized and tested for their cytotoxic effect against the oral cavity squamous-cell carcinoma (OSCC) cell lines CAL27 and SCC15. As a control, an immortalized and nontumorigenic cell line, Het-1A, was used. Linear peptides based on the RRWQWR core sequence showed a moderate cytotoxic effect and specificity towards tumorigenic cells. A tetrameric peptide, LfcinB(20–25)4, containing the RRWQWR motif, exhibited greater cytotoxic activity (>90%) in both OSCC cell lines compared to the linear lactoferricin peptide or the lactoferrin protein. Additionally, this tetrameric peptide showed the highest specificity towards tumorigenic cells among the tested peptides. Interestingly, this effect was very fast, with cell shrinkage, severe damage to cell membrane permeability, and lysis within one hour of treatment. Our results are consistent with a necrotic effect rather than an apoptotic one and suggest that this tetrameric peptide could be considered as a new candidate for the therapeutic treatment of OSCC.

Synergistic bactericide and antibiotic effects of dimeric, tetrameric, or palindromic peptides containing the RWQWR motif against Gram-positive and Gram-negative strains

“…The mixtures were centrifuged, the supernatants were collected, and the absorbance was determined to be 540 nm. 25 3 Results and discussion Linear, dimeric, and tetrameric peptides containing sequences derived from LfcinB (Table 1) were designed and synthesized through SPPS, using the Fmoc/tBu strategy. Dimeric peptides ((sequence) 2 -K-Ahx) were synthesized using the MAPs (multiple antigen peptides) methodology, and tetrameric peptides were obtained by oxidation of a precursor dimeric peptide whose sequence contained a C-terminal cysteine residue ((sequence) 2 -K-Ahx-C).…”

“…17,26 The linear, dimeric, and tetrameric peptides were obtained with high chromatographic purity, and the nal products had the expected monoisotopic mass. 17 Previously we reported the antibacterial activity of peptides containing LfcinB (20)(21)(22)(23)(24)(25), LcnB (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), and [Ala 19 ]-LfcinB (17-31) sequences against two E. coli strains (ATCC 25922 and 11 775). 17 It was established that dimeric and tetrameric peptides exhibited higher antibacterial activity than their monomeric analogue peptides.…”

“…Our results conrm that dimeric and tetrameric peptides derived from LfcinB (20-25) exhibited higher antibacterial activity against the evaluated strains than their monomeric counterpart. Furthermore, the tetrameric and dimeric peptides LfcinB (20)(21)(22)(23)(24)(25) 4 and LfcinB (20-25) 2 exhibited high antibacterial activity against all the tested E. coli strains; specically, their MICs ranged from 5 to 22 mM. Additionally, LfcinB (20)(21)(22)(23)(24)(25) 4 exhibited the highest antibacterial activity The results obtained in this investigation, together with our previous reports, indicate that polyvalence enhanced the antibacterial activity of LfcinB-derived sequences.…”

“…The tetrameric peptide containing the RRWQWR motif exhibited a bactericidal effect against the evaluated strains. Additionally, the peptides LfcinB (20)(21)(22)(23)(24)(25) 4 or LfcinB (20-25) 2 combined with vancomycin or ciprooxacin exhibited a signicant synergistic antibacterial effect.…”

Lactoferricin B reverses cisplatin resistance in head and neck squamous cell carcinoma cells through targeting PD‐L1

“…7,8 Lactoferricin B (LfcinB), cationic antimicrobial peptides, can selectively kill many types of tumor cells through targeting the cell membrane by electrostatic interactions with anionic molecules at the surfaces of cancer cells independent of multidrug-resistance mechanism. 9,10 As LfcinB was tested for the cytotoxic effect against the oral cavity squamous cell carcinoma and HNSCC cells, 11,12 LfcinB may offer hope to break down the chemoresistance of HNSCC while further investigations focused on mechanism are needed.…”