{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T16:13:47Z","timestamp":1783440827135,"version":"3.54.6"},"reference-count":96,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Antimicrobial peptides (AMPs) are natural bioactive peptides produced by all organisms\u2014from plants to insects, microbes and animals\u2014and constitute a first line of defense. As they exhibit a broad spectrum of activity (antibacterial, antiviral, antifungal, antiparasitic, anticancer), strong efforts are being made to integrate AMPs into clinical use. AMPs are also being investigated as anticancer agents to overcome the side effects and\/or resistance associated with current chemotherapies. In this context, we identified the natural AMP chionodracine from a new biological source: an Antarctic fish. Starting from the fragmentation of a chionodracine mutant peptide, a rational modular design approach was applied to develop three very short peptides (Pep-A, Pep-B and Pep-C), which were further modified with an N-terminal myristic acid lipid tail. The anticancer activity of the three N-myristoylated short peptides (Myr-A, Myr-B and Myr-C) was explored against the human cervical cancer HeLa cell line. The rationale behind this study is based on the previously reported antifungal activity of these myr peptides and on their ability to interact selectively with biological membrane-mimicking synthetic phospholipids without being particularly hemolytic or cytotoxic towards normal cells. We first demonstrated that myr peptides had cytotoxic activity against HeLa cells (IC50 from 32 to 47 \u03bcM) but spared healthy primary human fibroblasts, whereas the corresponding non-myr peptides failed to kill cancer cells. The peptide with no hemolytic activity and a low IC50, labeled Myr-B, was selected for subsequent analyses. Lactate dehydrogenase (LDH) assay and scanning electron microscopy (SEM) analysis revealed membrane damage and predominantly necrotic cell death in HeLa cells exposed to IC50 doses of the Myr-B peptide, compared with cells treated with Pep-B. To thoroughly investigate the molecular effects of Myr-B in HeLa cells, we employed high-resolution label-free shotgun quantitative proteomics coupled with bioinformatics. Our results showed that exposing HeLa cells to Myr-B led to the under-expression of proteins belonging to the \u201capoptosis- and splicing-associated protein complex\u201d, potentially influencing the alternative splicing process and consequently leading to a possible susceptibility to programmed cell death. These findings indicate that modifying natural AMPs may be a promising strategy for developing selective anticancer drugs and pinpoint Myr-B as an interesting target for future studies.<\/jats:p>","DOI":"10.3390\/ijms27093918","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:33:37Z","timestamp":1777376017000},"page":"3918","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Anticancer Activity of the Antimicrobial Myristoylated Peptide Myr-B in HeLa Cells: Cytotoxic, Membrane-Disruptive and Proteomic Insights"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6386-2009","authenticated-orcid":false,"given":"Michele","family":"Costanzo","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy"},{"name":"CEINGE\u2014Biotecnologie Avanzate Franco Salvatore, 80145 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Maiurano","sequence":"additional","affiliation":[{"name":"Department for Innovation in Biological, Agrofood and Forest Systems, University of Tuscia, 01100 Viterbo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6035-8213","authenticated-orcid":false,"given":"Marianna","family":"Caterino","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy"},{"name":"CEINGE\u2014Biotecnologie Avanzate Franco Salvatore, 80145 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Rita","family":"Taddei","sequence":"additional","affiliation":[{"name":"Center of Large Equipments, Section of Electron Microscopy, University of Tuscia, 01100 Viterbo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1848-1054","authenticated-orcid":false,"given":"Sabrina","family":"Bianco","sequence":"additional","affiliation":[{"name":"CEINGE\u2014Biotecnologie Avanzate Franco Salvatore, 80145 Naples, Italy"},{"name":"Department of Experimental and Clinical Medicine, University of Catanzaro Magna Gr\u00e6cia, Viale Europa, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6116-213X","authenticated-orcid":false,"given":"Simona","family":"Picchietti","sequence":"additional","affiliation":[{"name":"Department for Innovation in Biological, Agrofood and Forest Systems, University of Tuscia, 01100 Viterbo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8045-5651","authenticated-orcid":false,"given":"Francesco","family":"Buonocore","sequence":"additional","affiliation":[{"name":"Department for Innovation in Biological, Agrofood and Forest Systems, University of Tuscia, 01100 Viterbo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3054-7504","authenticated-orcid":false,"given":"Esther","family":"Imperlini","sequence":"additional","affiliation":[{"name":"Department for Innovation in Biological, Agrofood and Forest Systems, University of Tuscia, 01100 Viterbo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"108570","DOI":"10.1016\/j.biotechadv.2025.108570","article-title":"Advances in Antimicrobial Peptides: From Mechanistic Insights to Chemical Modifications","volume":"81","author":"Yang","year":"2025","journal-title":"Biotechnol. 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