The Invertebrate-Derived Antimicrobial Peptide Cm-p5 Induces Cell Death and ROS Production in Melanoma Cells.

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• Healthcare systems face challenges from multidrug-resistant pathogens and rising cancer incidence.
• Antimicrobial peptides (AMPs) show broad-spectrum activity, offering potential therapeutic alternatives.
• The α-helical peptide Cm-p5, previously studied for antifungal activity, had unexplored anti-cancer properties.

Purpose of the Study:

• To investigate the anti-cancer properties of the antimicrobial peptide Cm-p5.
• To explore the mechanism of action of Cm-p5 against cancer cell membranes.
• To evaluate the therapeutic potential of Cm-p5 for malignant melanoma treatment.

Main Methods:

• Calorimetry and molecular dynamics simulations to study peptide-membrane interactions.
• Cytotoxicity assays on A375 melanoma cells and non-malignant cells.
• Cell membrane integrity and function assays (DAPI/PI, DiSC3(5) staining).
• Apoptosis and reactive oxygen species (ROS) detection (Annexin V-FITC/PI assay).
• Cell proliferation assays to assess long-term effects.

Main Results:

• Cm-p5 demonstrated dose-dependent cytotoxic activity against A375 melanoma cells.
• No toxicity was observed against non-malignant cells or hemolytic activity.
• Cm-p5 induced permeabilization, disruption, and depolarization of melanoma cell membranes.
• Treatment with Cm-p5 led to cellular death via apoptosis and oxidative stress (ROS production).
• Cm-p5 significantly dampened A375 cell proliferation for several days post-treatment.

Conclusions:

• Cm-p5 exhibits significant anti-cancer activity against malignant melanoma.
• The peptide's mechanism involves direct damage to cancer cell membranes and induction of oxidative stress.
• Cm-p5 shows potential as a multifunctional therapeutic agent, possibly inhibiting melanoma recurrence.