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A. Morilla-Grasa, D. Andreu, M. A. Saornil, J. L. Ordonez, S. Nos-Barbera; In vitro Antitumoral Effect of Synthetic Peptides on Uveal Melanoma Cells. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4754.
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© ARVO (1962-2015); The Authors (2016-present)
To establish the antitumoral activity of four alfa-helix synthetic peptides from 11 to 15 aminoacid residues (aa) on two uveal melanoma cell lines (SP 6.5 and MKT-BR) with different metastatic potential and one melanocytic cell line (UW-1), compared to non-tumoral cells as control (corneal epithelial cell line, SIRC).
Peptides were synthesized by the solid-phase method as C-terminal carboxamides.A group of 11, 12 and 15 aa peptides were previously selected from a set of 150 antimicrobial peptides showing high antimicrobial activity. Inocula of forty thousand cells per well were distributed in 96-well plates, in octoplicates, of each cell line (SP 6.5, MKT-BR, UW-1, and SIRC) and exposed for 15 minutes to peptides in a range of concentration from10 to 100 µg/ml. Then, cell death was measured as mitochondrial activity by the XTT cytotoxicity test.
Fifteen aa peptide (KWKLFKKIGAVLKVL) at 10 µg/ml showed statistical differences between control group (SIRC cell line) and tumoral cells (SP 6.5 cell line). Eleven aa peptide (WKLFKKILKVL) showed differences in both tumoral and melanocytic cell lines at 10 µg/ml. Twelve aa peptides (WKKLFKKILKVL and KWKLFKKILKIL) showed statistical differences between control group and tumoral cells at 15, 30 and 60 µg/ml; one of these (KWKLFKKILKIL) showed also significative differences between control group and melanocytic cells (UW-1 cell line) at 30 and 60 µg/ml.
Based on the fact that alfa-helix peptides open ion-channels in membranes, we demonstrate that certain synthetic peptides, previously obtained to modulate antimicrobial activity, can be managed to interact as well with cell membranes of tumoral and non-tumoral cells, expressing different levels of activity. These peptides may account as potential antitumoral agents of therapeutic value in uveal melanoma treatment.
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