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Published on: June 7, 2019
The Invertebrate-Derived Antimicrobial Peptide Cm-p5 Induces Cell Death and ROS Production in Melanoma Cells
Ernesto M Martell-Huguet1,2, Daniel Alpízar-Pedraza3, Armando Rodriguez2,4
1Center for Protein Studies, Faculty of Biology, University of Havana, 25 and I, La Habana 10400, Cuba.
Abstract:
Nowadays, healthcare systems face two global challenges: the rise of multidrug-resistant pathogens and the growing incidence of cancer. Due to their broad spectrum of activities, antimicrobial peptides emerged as potential alternatives against both threats. Our group previously described the antifungal activity of the α-helical peptide Cm-p5, a derivative of the natural peptide Cm-p1, isolated from the coastal mollusk Cenchritis muricatus; however, its anti-cancer properties remained unexplored. Analyses through calorimetry and molecular dynamics simulations suggest the relevance of phosphatidylserine for the attachment of Cm-p5 to cancer cell membranes. Cm-p5 exhibited cytotoxic activity in a dose-dependent manner against A375 melanoma cells, without toxicity against non-malignant cells or hemolytic activity. DAPI/PI and DiSC3(5) staining confirmed permeabilization, disruption, and depolarization of A375 cytoplasmic membranes by Cm-p5. Furthermore, Annexin V-FITC/PI assay revealed the induction of cellular death in melanoma cells, which can result from the cumulative membrane damage and oxidative stress due to the overproduction of reactive oxygen species (ROS). Moreover, after the treatment, the proliferation of A375 cells was dampened for several days, suggesting that Cm-p5 might inhibit the recurrence of melanomas. These findings highlight the multifunctional nature of Cm-p5 and its potential for treating malignant melanoma.
Insights
Antimicrobial peptide Cm-p5 shows potent anti-cancer effects against melanoma cells. It disrupts cancer cell membranes and inhibits proliferation, offering a potential new treatment for malignant melanoma.
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.
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