ΔM4: Membrane-Active Peptide with Antitumoral Potential against Human Skin Cancer Cells

Peptides have become attractive potential agents due to their affinity to cancer cells. In this work, the biological activity of the peptide & UDelta;M4 against melanoma cancer cell line A375, epidermoid carcinoma cell line A431, and non-tumoral HaCaT cells was evaluated. The cytotoxic MTT assay demonstrates that & UDelta;M4 show five times more activity against cancer than non-cancer cells. The potential membrane effect of & UDelta;M4 was evaluated through lactate dehydrogenase release and Sytox uptake experiments. The results show a higher membrane activity of & UDelta;M4 against A431 in comparison with the A375 cell line at a level of 12.5 & mu;M. The Sytox experiments show that & UDelta;M4 has a direct effect on the permeability of cancer cells in comparison with control cells. Infrared spectroscopy was used to study the affinity of the peptide to membranes resembling the composition of tumoral and non-tumoral cells. The results show that & UDelta;M4 induces a fluidization effect on the tumoral lipid system over 5% molar concentration. Finally, to determine the appearance of phosphatidylserine on the surface of the cell, flow cytometry analyses were performed employing an annexin V-PE conjugate. The results suggest that 12.5 & mu;M of & UDelta;M4 induces phosphatidylserine translocation in A375 and A431 cancer cells. The findings of this study support the potential of & UDelta;M4 as a selective agent for targeting cancer cells. Its mechanism of action demonstrated selectivity, membrane-disrupting effects, and induction of phosphatidylserine translocation.

Automated summary

This study evaluated the biological activity of the peptide &UDelta;M4 against melanoma cancer cell line A375, epidermoid carcinoma cell line A431, and non-tumoral HaCaT cells. The results showed that &UDelta;M4 exhibited higher activity against cancer cells compared to non-cancer cells. It also demonstrated membrane-disrupting effects and induction of phosphatidylserine translocation, indicating its potential as a selective agent for targeting cancer cells.