{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:50:22Z","timestamp":1787496622129,"version":"build-2736575974"},"reference-count":47,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CAPES\u2014Foundation Coordination for the Improvement of Higher Education Personnel\u2014Cabral, LGC","award":["88887.630761\/2021-00"],"award-info":[{"award-number":["88887.630761\/2021-00"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The oral cavity is a frequent site for head and neck cancers, which rank as the sixth most common cancer globally, with a 5-year survival rate slightly over 50%. Current treatments are limited, and resistance to therapy remains a significant clinical obstacle. IsCT1, a membrane-active peptide derived from the venom of the scorpion Opisthacanthus madagascariensis, has shown antitumor effects in various cancer cell lines, including breast cancer and chronic myeloid leukemia. However, its hemolytic action limits its potential therapeutic use. This study aims to assess the antitumor and antiproliferative activities of synthetic peptides derived from IsCT1 (IsCT-P, AC-AFPK-IsCT1, AFPK-IsCT1, AC-KKK-IsCT1, and KKK-IsCT1) in the context of oral squamous cell carcinoma. We evaluated the cytotoxic effects of these peptides on tongue squamous cell carcinoma cells and normal cells, as well as their impact on cell cycle phases, the expression of proliferation markers, modulators of cell death pathways, and mitochondrial potential. Our results indicate that the IsCT1 derivatives IsCT-P and AC-AFPK-IsCT1 possess cytotoxic properties towards squamous cell carcinoma cells, reducing mitochondrial membrane potential and the proliferative index. The treatment of cancer cells with AC-AFPK-IsCT1 led to a positive modulation of pro-apoptotic markers p53 and caspases 3 and 8, a decrease in PCNA and Cyclin D1 expression, and cell cycle arrest in the S phase. Notably, contrary to the parental IsCT1 peptide, AC-AFPK-IsCT1 did not exhibit hemolytic activity or cytotoxicity towards normal cells. Therefore, AC-AFPK-IsCT1 might be a viable therapeutic option for head and neck cancer treatment.<\/jats:p>","DOI":"10.3390\/molecules29194533","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T10:41:47Z","timestamp":1727174507000},"page":"4533","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Antitumoral and Antiproliferative Potential of Synthetic Derivatives of Scorpion Peptide IsCT1 in an Oral Cavity Squamous Carcinoma Model"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4586-2945","authenticated-orcid":false,"given":"Laertty Garcia de Sousa","family":"Cabral","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of Sao Paulo, Sao Paulo 05508-220, Brazil"},{"name":"Laboratory of Development and Innovation, Butantan Institute, Sao Paulo 05585-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2049-7627","authenticated-orcid":false,"given":"Cyntia Silva","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Paulista School of Medicine, Postgraduate Program in Molecular Biology, Federal University of S\u00e3o Paulo, Sao Paulo 04044-020, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9420-0956","authenticated-orcid":false,"suffix":"Jr.","given":"Vani Xavier","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Paulista School of Medicine, Postgraduate Program in Molecular Biology, Federal University of S\u00e3o Paulo, Sao Paulo 04044-020, Brazil"},{"name":"Center for Natural and Human Sciences, Federal University of ABC, Santo Andre 09280-560, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosely Cabette Barbosa","family":"Alves","sequence":"additional","affiliation":[{"name":"Laboratory of Development and Innovation, Butantan Institute, Sao Paulo 05585-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3747-255X","authenticated-orcid":false,"given":"Jean-Luc","family":"Poyet","sequence":"additional","affiliation":[{"name":"INSERM UMRS976, Institut De Recherche Saint-Louis, H\u00f4pital Saint-Louis, 75010 Paris, France"},{"name":"Universit\u00e9 Paris Cit\u00e9, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Durvanei Augusto","family":"Maria","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Sao Paulo, Sao Paulo 05508-220, Brazil"},{"name":"Laboratory of Development and Innovation, Butantan Institute, Sao Paulo 05585-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bouaoud, J., Bossi, P., Elkabets, M., Schmitz, S., van Kempen, L.C., Martinez, P., Jagadeeshan, S., Breuskin, I., Puppels, G.J., and Hoffmann, C. 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