Synthetic Peptide ΔM4-Induced Cell Death Associated with Cytoplasmic Membrane Disruption, Mitochondrial Dysfunction and Cell Cycle Arrest in Human Melanoma Cells
Melanoma is the most dangerous and lethal form of skin cancer, due to its ability to spread to different organs if it is not treated at an early stage. Conventional chemotherapeutics are failing as a result of drug resistance and weak tumor selectivity. Therefore, efforts to evaluate novel molecules...
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MDPI AG
2020-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/23/5684 |
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| author | Gloria A. Santa-González Edwin Patiño-González Marcela Manrique-Moreno |
| author_facet | Gloria A. Santa-González Edwin Patiño-González Marcela Manrique-Moreno |
| author_sort | Gloria A. Santa-González |
| collection | DOAJ |
| description | Melanoma is the most dangerous and lethal form of skin cancer, due to its ability to spread to different organs if it is not treated at an early stage. Conventional chemotherapeutics are failing as a result of drug resistance and weak tumor selectivity. Therefore, efforts to evaluate novel molecules for the treatment of skin cancer are necessary. Antimicrobial peptides have become attractive anticancer agents because they execute their biological activity with features such as a high potency of action, a wide range of targets, and high target specificity and selectivity. In the present study, the antiproliferative activity of the synthetic peptide ΔM4 on A375 human melanoma cells and spontaneously immortalized HaCaT human keratinocytes was investigated. The cytotoxic effect of ΔM4 treatment was evaluated through propidium iodide uptake by flow cytometry. The results indicated selective toxicity in A375 cells and, in order to further investigate the mode of action, assays were carried out to evaluate morphological changes, mitochondrial function, and cell cycle progression. The findings indicated that ΔM4 exerts its antitumoral effects by multitarget action, causing cell membrane disruption, a change in the mitochondrial transmembrane potential, an increase of reactive oxygen species, and cell cycle accumulation in S-phase. Further exploration of the peptide may be helpful in the design of novel anticancer peptides. |
| first_indexed | 2024-03-10T14:23:06Z |
| format | Article |
| id | doaj.art-2b538d18b36548daa29659b5a896c1d5 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T14:23:06Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-2b538d18b36548daa29659b5a896c1d52023-11-20T23:13:49ZengMDPI AGMolecules1420-30492020-12-012523568410.3390/molecules25235684Synthetic Peptide ΔM4-Induced Cell Death Associated with Cytoplasmic Membrane Disruption, Mitochondrial Dysfunction and Cell Cycle Arrest in Human Melanoma CellsGloria A. Santa-González0Edwin Patiño-González1Marcela Manrique-Moreno2Structural Biochemistry of Macromolecules Group, Chemistry Institute, Faculty of Exact and Natural Sciences, University of Antioquia, Medellin A.A. 1226, ColombiaStructural Biochemistry of Macromolecules Group, Chemistry Institute, Faculty of Exact and Natural Sciences, University of Antioquia, Medellin A.A. 1226, ColombiaStructural Biochemistry of Macromolecules Group, Chemistry Institute, Faculty of Exact and Natural Sciences, University of Antioquia, Medellin A.A. 1226, ColombiaMelanoma is the most dangerous and lethal form of skin cancer, due to its ability to spread to different organs if it is not treated at an early stage. Conventional chemotherapeutics are failing as a result of drug resistance and weak tumor selectivity. Therefore, efforts to evaluate novel molecules for the treatment of skin cancer are necessary. Antimicrobial peptides have become attractive anticancer agents because they execute their biological activity with features such as a high potency of action, a wide range of targets, and high target specificity and selectivity. In the present study, the antiproliferative activity of the synthetic peptide ΔM4 on A375 human melanoma cells and spontaneously immortalized HaCaT human keratinocytes was investigated. The cytotoxic effect of ΔM4 treatment was evaluated through propidium iodide uptake by flow cytometry. The results indicated selective toxicity in A375 cells and, in order to further investigate the mode of action, assays were carried out to evaluate morphological changes, mitochondrial function, and cell cycle progression. The findings indicated that ΔM4 exerts its antitumoral effects by multitarget action, causing cell membrane disruption, a change in the mitochondrial transmembrane potential, an increase of reactive oxygen species, and cell cycle accumulation in S-phase. Further exploration of the peptide may be helpful in the design of novel anticancer peptides.https://www.mdpi.com/1420-3049/25/23/5684melanoma skin cancerantimicrobial peptidesantiproliferative peptidescell cycle arrestmembrane integrity |
| spellingShingle | Gloria A. Santa-González Edwin Patiño-González Marcela Manrique-Moreno Synthetic Peptide ΔM4-Induced Cell Death Associated with Cytoplasmic Membrane Disruption, Mitochondrial Dysfunction and Cell Cycle Arrest in Human Melanoma Cells Molecules melanoma skin cancer antimicrobial peptides antiproliferative peptides cell cycle arrest membrane integrity |
| title | Synthetic Peptide ΔM4-Induced Cell Death Associated with Cytoplasmic Membrane Disruption, Mitochondrial Dysfunction and Cell Cycle Arrest in Human Melanoma Cells |
| title_full | Synthetic Peptide ΔM4-Induced Cell Death Associated with Cytoplasmic Membrane Disruption, Mitochondrial Dysfunction and Cell Cycle Arrest in Human Melanoma Cells |
| title_fullStr | Synthetic Peptide ΔM4-Induced Cell Death Associated with Cytoplasmic Membrane Disruption, Mitochondrial Dysfunction and Cell Cycle Arrest in Human Melanoma Cells |
| title_full_unstemmed | Synthetic Peptide ΔM4-Induced Cell Death Associated with Cytoplasmic Membrane Disruption, Mitochondrial Dysfunction and Cell Cycle Arrest in Human Melanoma Cells |
| title_short | Synthetic Peptide ΔM4-Induced Cell Death Associated with Cytoplasmic Membrane Disruption, Mitochondrial Dysfunction and Cell Cycle Arrest in Human Melanoma Cells |
| title_sort | synthetic peptide δm4 induced cell death associated with cytoplasmic membrane disruption mitochondrial dysfunction and cell cycle arrest in human melanoma cells |
| topic | melanoma skin cancer antimicrobial peptides antiproliferative peptides cell cycle arrest membrane integrity |
| url | https://www.mdpi.com/1420-3049/25/23/5684 |
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