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.
Highlights
Oral squamous-cell carcinoma (OSCC) is fatal in approximately 50% of the diagnosed cases [1]
LfcinB25 and its derived peptides may offer a therapeutic alternative for the treatment of OSCC, with higher selectivity towards cancer cells [41, 46, 48], an important advantage compared to the standard treatments [49, 50]
We tested the cytotoxic activity of LfB, LfcinB25, and LfcinB25-derived peptides in the OSCC cell lines CAL27 and SCC15, using the Het-1A cell line as control
Summary
Oral squamous-cell carcinoma (OSCC) is fatal in approximately 50% of the diagnosed cases [1]. It can be controlled during the early stages of the disease; it is considered to be of poor prognosis with low survival rate in advanced stages (12% on average) [2,3,4]. Lf anticancer effects have been evaluated for different types of cancer using both in vitro and in vivo models [13,14,15,16,17,18,19,20,21], whereby it was determined that bovine Lf (LfB) exhibits greater cytotoxic activity than human Lf (LfH) [22]. In breast and in head and neck cancers, it has been reported that LfB inhibits cell proliferation by arresting cancer cells in the G1-G0 phase of the cell cycle and by increasing the expression of proinflammatory and immune
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