Synthetic Peptide ΔM4-Induced Cell Death Associated with Cytoplasmic Membrane Disruption, Mitochondrial Dysfunction and Cell Cycle Arrest in Human Melanoma Cells
| Autor: | Marcela Manrique-Moreno, Edwin Patiño-González, Gloria A. Santa-González |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Programmed cell death
Skin Neoplasms Cell cycle checkpoint Antimicrobial peptides Pharmaceutical Science Antineoplastic Agents Apoptosis Article Analytical Chemistry melanoma skin cancer antiproliferative peptides Cell membrane lcsh:QD241-441 03 medical and health sciences chemistry.chemical_compound antimicrobial peptides 0302 clinical medicine lcsh:Organic chemistry Drug Discovery Tumor Cells Cultured medicine Humans Propidium iodide Physical and Theoretical Chemistry Melanoma Cell Proliferation 030304 developmental biology Membrane Potential Mitochondrial 0303 health sciences Cell Death Cell Membrane Organic Chemistry Cell Cycle Checkpoints Cell cycle medicine.disease Mitochondria HaCaT medicine.anatomical_structure chemistry Chemistry (miscellaneous) cell cycle arrest membrane integrity 030220 oncology & carcinogenesis Cancer research Molecular Medicine Peptides Reactive Oxygen Species Signal Transduction |
| Zdroj: | Molecules Volume 25 Issue 23 Molecules, Vol 25, Iss 5684, p 5684 (2020) |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules25235684 |
| Popis: | 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 &Delta M4 on A375 human melanoma cells and spontaneously immortalized HaCaT human keratinocytes was investigated. The cytotoxic effect of &Delta M4 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 &Delta M4 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. |
| Databáze: | OpenAIRE |
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