The Invertebrate-Derived Antimicrobial Peptide Cm-p5 Induces Cell Death and ROS Production in Melanoma Cells
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 antifun...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
|
| Series: | Marine Drugs |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1660-3397/23/7/273 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1839615686138134528 |
|---|---|
| author | Ernesto M. Martell-Huguet Daniel Alpízar-Pedraza Armando Rodriguez Marc Zumwinkel Mark Grieshober Fidel Morales-Vicente Ann-Kathrin Kissmann Markus Krämer Steffen Stenger Octavio L. Franco Ludger Ständker Anselmo J. Otero-Gonzalez Frank Rosenau |
| author_facet | Ernesto M. Martell-Huguet Daniel Alpízar-Pedraza Armando Rodriguez Marc Zumwinkel Mark Grieshober Fidel Morales-Vicente Ann-Kathrin Kissmann Markus Krämer Steffen Stenger Octavio L. Franco Ludger Ständker Anselmo J. Otero-Gonzalez Frank Rosenau |
| author_sort | Ernesto M. Martell-Huguet |
| collection | DOAJ |
| description | 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 <i>Cenchritis muricatus</i>; 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. |
| format | Article |
| id | doaj-art-72e29c8c8b2d49baaa6ee44849bbd9d3 |
| institution | Matheson Library |
| issn | 1660-3397 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj-art-72e29c8c8b2d49baaa6ee44849bbd9d32025-07-25T13:28:48ZengMDPI AGMarine Drugs1660-33972025-06-0123727310.3390/md23070273The Invertebrate-Derived Antimicrobial Peptide Cm-p5 Induces Cell Death and ROS Production in Melanoma CellsErnesto M. Martell-Huguet0Daniel Alpízar-Pedraza1Armando Rodriguez2Marc Zumwinkel3Mark Grieshober4Fidel Morales-Vicente5Ann-Kathrin Kissmann6Markus Krämer7Steffen Stenger8Octavio L. Franco9Ludger Ständker10Anselmo J. Otero-Gonzalez11Frank Rosenau12Center for Protein Studies, Faculty of Biology, University of Havana, 25 and I, La Habana 10400, CubaCenter for Pharmaceutical Research and Development, 26th Avenue, No 1605, Nuevo Vedado, La Habana 10400, CubaCore Facility for Functional Peptidomics, Ulm Peptide Pharmaceuticals (U-PEP), Faculty of Medicine, Ulm University, 89081 Ulm, GermanyInstitute of Medical Microbiology and Hygiene, University Clinic of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, GermanyInstitute of Medical Microbiology and Hygiene, University Clinic of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, GermanySynthetic Peptides Group, Center for Genetic Engineering and Biotechnology, La Habana 10600, CubaInstitute of Pharmaceutical Biotechnology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, GermanyInstitute of Pharmaceutical Biotechnology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, GermanyInstitute of Medical Microbiology and Hygiene, University Clinic of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, GermanyCenter for Biochemical and Proteomics Analyses, Catholic University of Brasilia, Brasilia 71966-700, BrazilCore Facility for Functional Peptidomics, Ulm Peptide Pharmaceuticals (U-PEP), Faculty of Medicine, Ulm University, 89081 Ulm, GermanyCenter for Protein Studies, Faculty of Biology, University of Havana, 25 and I, La Habana 10400, CubaInstitute of Pharmaceutical Biotechnology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, GermanyNowadays, 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 <i>Cenchritis muricatus</i>; 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.https://www.mdpi.com/1660-3397/23/7/273Cm-p5anti-cancer peptidemembrane disruptioncell deathROS |
| spellingShingle | Ernesto M. Martell-Huguet Daniel Alpízar-Pedraza Armando Rodriguez Marc Zumwinkel Mark Grieshober Fidel Morales-Vicente Ann-Kathrin Kissmann Markus Krämer Steffen Stenger Octavio L. Franco Ludger Ständker Anselmo J. Otero-Gonzalez Frank Rosenau The Invertebrate-Derived Antimicrobial Peptide Cm-p5 Induces Cell Death and ROS Production in Melanoma Cells Marine Drugs Cm-p5 anti-cancer peptide membrane disruption cell death ROS |
| title | The Invertebrate-Derived Antimicrobial Peptide Cm-p5 Induces Cell Death and ROS Production in Melanoma Cells |
| title_full | The Invertebrate-Derived Antimicrobial Peptide Cm-p5 Induces Cell Death and ROS Production in Melanoma Cells |
| title_fullStr | The Invertebrate-Derived Antimicrobial Peptide Cm-p5 Induces Cell Death and ROS Production in Melanoma Cells |
| title_full_unstemmed | The Invertebrate-Derived Antimicrobial Peptide Cm-p5 Induces Cell Death and ROS Production in Melanoma Cells |
| title_short | The Invertebrate-Derived Antimicrobial Peptide Cm-p5 Induces Cell Death and ROS Production in Melanoma Cells |
| title_sort | invertebrate derived antimicrobial peptide cm p5 induces cell death and ros production in melanoma cells |
| topic | Cm-p5 anti-cancer peptide membrane disruption cell death ROS |
| url | https://www.mdpi.com/1660-3397/23/7/273 |
| work_keys_str_mv | AT ernestommartellhuguet theinvertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT danielalpizarpedraza theinvertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT armandorodriguez theinvertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT marczumwinkel theinvertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT markgrieshober theinvertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT fidelmoralesvicente theinvertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT annkathrinkissmann theinvertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT markuskramer theinvertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT steffenstenger theinvertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT octaviolfranco theinvertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT ludgerstandker theinvertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT anselmojoterogonzalez theinvertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT frankrosenau theinvertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT ernestommartellhuguet invertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT danielalpizarpedraza invertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT armandorodriguez invertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT marczumwinkel invertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT markgrieshober invertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT fidelmoralesvicente invertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT annkathrinkissmann invertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT markuskramer invertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT steffenstenger invertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT octaviolfranco invertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT ludgerstandker invertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT anselmojoterogonzalez invertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells AT frankrosenau invertebratederivedantimicrobialpeptidecmp5inducescelldeathandrosproductioninmelanomacells |