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Updated: Mar 29, 2026
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Melanoma cell surface-expressed phosphatidylserine as a therapeutic target for cationic anticancer peptide,
Che Wang1,2, Yin-Wang Chen1, Liang Zhang1
1a Department of Pharmacy , School of Chemistry and Chemical Engineering, Liaoning Normal University , Dalian , China and.
Abstract:
We have previously reported that temporin-1CEa, a cationic antimicrobial peptide, exerts preferential cytotoxicity toward cancer cells. However, the exact molecular mechanism for this cancer-selectivity is still largely unknown. Here, we found that the negatively charged phosphatidylserine (PS) expressed on cancer cell surface serves as a target for temporin-1CEa. Our results indicate that human A375 melanoma cells express 50-fold more PS than non-cancerous HaCaT cells. The expression of cell surface PS in various cancer cell lines closely correlated with their ability to be recognized, bound and killed by temporin-1CEa. Additionally, the cytotoxicity of temporin-1CEa against A375 cells can be ameliorated by annexin V, which binds to cell surface PS with high affinity. Moreover, the data of isothermal titration calorimetry assay further confirmed a direct binding of temporin-1CEa to PS, at a ratio of 1:5 (temporin-1CEa:PS). Interestingly, the circular dichroism spectra analysis using artificial biomembrane revealed that PS not only provides electrostatic attractive sites for temporin-1CEa but also confers the membrane-bound temporin-1CEa to form α-helical structure, therefore, enhances the affinity and membrane disrupting ability of temporin-1CEa. In summary, these findings suggested that the melanoma cells expressed PS may serve as a promising target for temporin-1CEa or other cationic anticancer peptides.
Insights
Temporin-1CEa, a peptide, targets cancer cells by binding to phosphatidylserine (PS). This interaction enhances the peptide's ability to disrupt cancer cell membranes, offering a potential therapeutic strategy.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Temporin-1CEa, a cationic antimicrobial peptide, shows preferential cytotoxicity against cancer cells.
- The precise molecular mechanisms underlying this cancer selectivity remain largely undetermined.
Purpose of the Study:
- To elucidate the molecular mechanism behind temporin-1CEa's selective cancer cell cytotoxicity.
- To identify the specific molecular target of temporin-1CEa on cancer cell surfaces.
Main Methods:
- Comparative analysis of phosphatidylserine (PS) expression on cancer versus non-cancerous cells.
- Assessment of temporin-1CEa's cytotoxicity and binding affinity in relation to PS expression.
- Isothermal titration calorimetry and circular dichroism spectroscopy to study temporin-1CEa-PS interactions.
Main Results:
- Cancer cells, including melanoma, exhibit significantly higher surface PS expression compared to normal cells.
- Temporin-1CEa's binding to and cytotoxicity against cancer cells directly correlate with PS levels.
- PS binding induces an alpha-helical structure in temporin-1CEa, enhancing its membrane-disrupting capabilities.
Conclusions:
- Phosphatidylserine (PS) on cancer cell surfaces is a key molecular target for temporin-1CEa.
- The interaction with PS enhances temporin-1CEa's anticancer activity by promoting membrane disruption.
- Targeting cell surface PS presents a promising strategy for developing temporin-1CEa or similar cationic peptides as cancer therapeutics.
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