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

Solarte VA, Rosas JE, Rivera ZJ, Arango-Rodríguez ML, García JE, Vernot JP - Biomed Res Int (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Cellular and Molecular Physiology Group, Biomedical Research Institute, Faculty of Medicine, Universidad Nacional de Colombia, Bogotá 111321, Colombia.

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.

No MeSH data available.


Related in: MedlinePlus

Cell morphology of CAL27 (a) and SCC15 (b) after treatment with LfcinB(20–25)4 for 1, 12, or 24 h. The STA concentration used was 0.86 μM (0.4 μg/mL) for CAL27 and 1.29 μM (0.6 μg/mL) for SCC15. Photomicrographs were taken with a phase-contrast microscope.
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fig6: Cell morphology of CAL27 (a) and SCC15 (b) after treatment with LfcinB(20–25)4 for 1, 12, or 24 h. The STA concentration used was 0.86 μM (0.4 μg/mL) for CAL27 and 1.29 μM (0.6 μg/mL) for SCC15. Photomicrographs were taken with a phase-contrast microscope.

Mentions: Given this rapid effect, the PI permeability in peptide-treated OSCC cells was evaluated (Figure 5). In the case of the SCC15 cell line, this evaluation was done for the two distinctive morphological cell populations observed in continuous culture independent of cell confluence (Supplementary Figure 1). These mesenchymal- and epithelial-like phenotypes were confirmed by the expression of phenotype-specific markers (Supplementary Figure 2). LfB, LfcinB25, and LfcinB(20–25) peptide had minimum effect, if any, on cell permeability in both cell lines. LfcinB-Pal has only a minimum effect in the CAL27 cell line, while it did not show any effect in the SCC15. On the contrary, LfcinB(20–25)4 exhibited an important lytic effect on both cell lines. On comparing the SCC15 cell phenotypes, the mesenchymal-like phenotype was found to be highly sensitive to the tetramer treatment (Figure 5). Interestingly, this effect was observed after only 1 h of treatment, which agrees with the previous cell viability assays (Figure 4). Morphological changes associated with LfcinB(20–25)4 treatment were seen almost immediately in terms of cell shrinkage in CAL27 and SCC15 from the first hour of treatment, while very few cells retained their morphology (Figure 6).


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

Solarte VA, Rosas JE, Rivera ZJ, Arango-Rodríguez ML, García JE, Vernot JP - Biomed Res Int (2015)

Cell morphology of CAL27 (a) and SCC15 (b) after treatment with LfcinB(20–25)4 for 1, 12, or 24 h. The STA concentration used was 0.86 μM (0.4 μg/mL) for CAL27 and 1.29 μM (0.6 μg/mL) for SCC15. Photomicrographs were taken with a phase-contrast microscope.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4644816&req=5

fig6: Cell morphology of CAL27 (a) and SCC15 (b) after treatment with LfcinB(20–25)4 for 1, 12, or 24 h. The STA concentration used was 0.86 μM (0.4 μg/mL) for CAL27 and 1.29 μM (0.6 μg/mL) for SCC15. Photomicrographs were taken with a phase-contrast microscope.
Mentions: Given this rapid effect, the PI permeability in peptide-treated OSCC cells was evaluated (Figure 5). In the case of the SCC15 cell line, this evaluation was done for the two distinctive morphological cell populations observed in continuous culture independent of cell confluence (Supplementary Figure 1). These mesenchymal- and epithelial-like phenotypes were confirmed by the expression of phenotype-specific markers (Supplementary Figure 2). LfB, LfcinB25, and LfcinB(20–25) peptide had minimum effect, if any, on cell permeability in both cell lines. LfcinB-Pal has only a minimum effect in the CAL27 cell line, while it did not show any effect in the SCC15. On the contrary, LfcinB(20–25)4 exhibited an important lytic effect on both cell lines. On comparing the SCC15 cell phenotypes, the mesenchymal-like phenotype was found to be highly sensitive to the tetramer treatment (Figure 5). Interestingly, this effect was observed after only 1 h of treatment, which agrees with the previous cell viability assays (Figure 4). Morphological changes associated with LfcinB(20–25)4 treatment were seen almost immediately in terms of cell shrinkage in CAL27 and SCC15 from the first hour of treatment, while very few cells retained their morphology (Figure 6).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Cellular and Molecular Physiology Group, Biomedical Research Institute, Faculty of Medicine, Universidad Nacional de Colombia, Bogotá 111321, Colombia.

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.

No MeSH data available.


Related in: MedlinePlus