A tetrameric peptide derived from bovine lactoferricin as a potential therapeutic tool for oral squamous cell carcinoma: A preclinical model

Abstract

Oral squamous cell carcinoma is the fifth most common epithelial cancer in the world, and its current clinical treatment has both low efficiency and poor selectivity. Cationic amphipathic peptides have been proposed as new drugs for the treatment of different types of cancer. The main goal of the present work was to determine the potential of LfcinB(20–25)4, a tetrameric peptide based on the core sequence RRWQWR of bovine lactoferricin LfcinB(20–25), for the treatment of OSCC. In brief, OSCC was induced in the buccal pouch of hamsters by applying 7,12-Dimethylbenz(a)anthracene, and tumors were treated with one of the following peptides: LfcinB(20–25)4, LfcinB(20–25), or vehicle (control). Lesions were macroscopically evaluated every two days and both histological and serum IgG assessments were conducted after 5 weeks. The size of the tumors treated with LfcinB(20–25)4 and LfcinB(20–25) was smaller than that of the control group (46.16±4.41 and 33.92±2.74 mm3 versus 88.77±10.61 mm3, respectively). Also, LfcinB(20–25)4 caused acellularity in the parenchymal tumor compared with LfcinB(20–25) and vehicle treatments. Furthermore, our results demonstrated that both LfcinB(20–25)4 and LfcinB(20–25) induced higher degree of apoptosis relative to the untreated tumors (75–86% vs 8%, respectively). Moreover, although the lowest inflammatory response was achieved when LfcinB(20–25)4 was used, this peptide appeared to induce higher levels of IgG antibodies relative to the vehicle and LfcinB(20–25). In addition the cellular damage and selectivity of the LfcinB(20–25)4 peptide was evaluated in vitro. These assays showed that LfcinB(20–25)4 triggers a selective necrotic effect in the carcinoma cell line. Cumulatively, these data indicate that LfcinB(20–25)4 could be considered as a new therapeutic agent for the treatment of OSCC.

The tetrameric peptide LfcinB (20–25)4 derived from bovine lactoferricin induces apoptosis in the MCF-7 breast cancer cell line

“…30,31 On the other hand, this peptide also exhibited a selective cytotoxic effect against OSCC-derived cell lines CAL-27 (IC 50 ¼ 9 mM) and SCC15 (IC 50 ¼ 9 mM), while the peptide's cytotoxic effect against the non-tumorigenic cell line was moderate. 28,29 It can be seen that these IC 50 values are of the same order of magnitude as those obtained for MCF-7 cells, which conrms that the peptide exhibited signicantly selective cytotoxic effect against human cell lines derived from breast and oral cancer. The cytotoxic effect of the peptide against MCF-7, CAL-27, and SCC-15 cancer cells continues for 24 h aer treatment, suggesting that the peptide's cytotoxic effect against cancer cells lines could be broad spectrum.…”

“…These results are in agreement with previous studies that suggest that the cytotoxic effect of LfcinB or peptides derived from LfcinB could be mediated by both apoptosis and/or necrosis. 28 It has also been shown that this duality in the action mechanism is dependent on the peptide concentration. The anti-tumoral activity of the tetrameric peptide LfcinB (20)(21)(22)(23)(24)(25) 4 in a hamster model was related to both apoptotic and necrotic processes; 28 the antitumoral activity of animals chronically treated with tetrameric peptide at higher concentrations was mediated mainly by apoptosis.…”

“…The cytotoxic effect of the peptide against MCF-7, CAL-27, and SCC-15 cancer cells continues for 24 h aer treatment, suggesting that the peptide's cytotoxic effect against cancer cells lines could be broad spectrum. 28,29 The tetrameric peptide LfcinB (20-25) 4 is a tetra-branched molecule containing the minimal motif RRWQWR in each branch. In a similar way, in addition to the tetrameric peptide LfcinB (20-25) 4 , other polyvalent peptides (dimeric and tetrameric peptides) containing RRWQWRMKLG and FKARRWQWRMKKLG sequences, which include the minimal motif, also exhibited a signicant selective cytotoxic effect against breast cancer cells MDA-MB-468 and MDA-MB-231, suggesting that the polyvalence of the RRWQWR sequence is relevant for the cytotoxic effect against breast cancer cells.…”

“…In an in vivo model, this peptide exhibited antitumoral activity, which was associated with apoptotic and necrotic processes. 28 This peptide also exhibited a signicant cytotoxic effect against MDA-MB-468 (IC 50 ¼ 6 mM) and MDA-MB-231 (IC 50 ¼ 15 mM) breast cancer cell lines. It was observed that cell viability was near zero when cells were treated with the tetrameric peptide at 11 mM.…”

Pullulan nanofibers containing the antimicrobial palindromic peptide LfcinB (21–25)Palobtainedviaelectrospinning

“…26 In previous reports, it has been demonstrated that short synthetic peptides exhibited higher antibacterial, antifungal, and anticancerigenic activity than LfcinB. [26][27][28][29][30][31] The palindromic peptide LfcinB (21-25) Pal : RWQWRWQWR is a promising peptide for developing new therapeutic agents. [26][27][28][29][30] This peptide exhibits antibacterial activity against Grampositive and Gram-negative bacteria and fungi and a cytotoxic effect against oral carcinoma and breast cancer cell lines.…”