MPX (Mastoparan X) and MP1 (Polybia-MP1) are cationic amphiphilic peptides isolated from the venom of insects of the Vespidae family. Due to their physicochemical features, these peptides show affinity for biomimetic membranes, especially the more anionic ones. In this study, we investigated the cell-selective effects of MPX and MP1 peptides, comparing their cytotoxicity and metabolic effects on melanocytes and their respective counterparts, melanoma cells. By employing UV-vis spectroscopy and fluorescence microscopy assays, we provided mechanistic insights into these peptides' antimelanoma activity. MPX and MP1 peptides were cytotoxic to both cell lines. However, their effect was more intense in melanoma than in melanocyte cells. Both cell lines treated with MPX and MP1 peptides showed phosphatidylserine externalization. However, unlike MP1 treatment, MPX also elicited pore formation in the plasma membranes of melanoma cells. These data indicate that the mode of action of MPX and MP1 involves different processes, namely, necrosis and apoptosis, respectively. The levels of reactive oxygen species did not undergo significant changes, but intracellular calcium levels increased considerably in melanoma cells treated with MPX. Both cell lines have their mitochondrial membrane potentials decreased after peptide treatments; nonetheless, this reduction was more intense in melanoma than in melanocyte cells. Altogether, these data reveal that the MPX and MP1 peptides are selective for melanoma tumorigenic cells, reassuring their antimelanoma therapeutic potential. Despite their structural similarities, these peptides have cell-type-relatable distinct modes of action, which resonate in both plasma membrane alterations and metabolic processes, indicating that these effects are not mutually exclusive and not the same for all cells and conditions.
Semerdjian et al. (Fri,) studied this question.
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