{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T21:03:08Z","timestamp":1779310988821,"version":"3.51.4"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T00:00:00Z","timestamp":1749945600000},"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","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>Head and neck squamous cell carcinoma (SCC), particularly in the oral cavity, is among the most prevalent and lethal forms of cancer globally. Current therapeutic strategies, predominantly involving cisplatin, face challenges like chemoresistance and toxicity to normal cells, justifying the exploration of new approaches. This study evaluates the antitumor, antiproliferative, and immunomodulatory potential of a synthetic peptide derived from IsCT1 (Isalo scorpion cytotoxic peptide), named AC-AFPK-IsCT1, in combination with cisplatin in oral squamous cell carcinoma cellular models. Tumor and normal cells were treated with varying concentrations of cisplatin and peptide, and the cytotoxicity was measured through an MTT assay, while apoptosis and cell cycle alterations were assessed via flow cytometry. Interestingly, the combination of AC-AFPK-IsCT1 with cisplatin exhibited higher specificity for tumor cells, significantly reducing IC50 values compared to cisplatin used as a single agent. Moreover, the combination treatment induced pronounced S-phase cell cycle arrest and enhanced apoptotic activity, evidenced by the upregulation of caspase-3, caspase-8, and p53, while maintaining low toxicity in normal fibroblast cells. The peptide also modulated the mitochondrial membrane potential, further contributing to the activation of intrinsic apoptotic pathways. The data suggest that AC-AFPK-IsCT1 potentiates the antitumor effects of cisplatin by engaging both intrinsic and extrinsic apoptotic pathways while preserving normal cell viability. These findings underscore the potential of combining cisplatin with AC-AFPK-IsCT1 as a promising therapeutic strategy for improving the efficacy of chemotherapy in SCC, reducing systemic toxicity, and overcoming chemoresistance.<\/jats:p>","DOI":"10.3390\/molecules30122594","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T05:28:33Z","timestamp":1750051713000},"page":"2594","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Evaluation of the Antitumor and Antiproliferative Potential of Synthetic Peptides Derived from IsCT1, Associated with Cisplatin, in Squamous Cell Carcinoma of the Oral Cavity"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4586-2945","authenticated-orcid":false,"given":"Laertty Garcia de Sousa","family":"Cabral","sequence":"first","affiliation":[{"name":"Laboratory of Development and Innovation, Butantan Institute, Sao Paulo 05585-000, Brazil"},{"name":"Faculty of Medicine, University of Sao Paulo (FMUSP), Sao Paulo 05508-220, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2049-7627","authenticated-orcid":false,"given":"Cyntia Silva","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Federal University of Sao Paulo (UNIFESP) Sao Paulo 09913-030, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9420-0956","authenticated-orcid":false,"suffix":"Jr.","given":"Vani Xavier","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Federal University of Sao Paulo (UNIFESP) Sao Paulo 09913-030, Brazil"},{"name":"Center for Natural and Human Sciences, Federal University of ABC, Santo Andre 09210-580, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4187-8092","authenticated-orcid":false,"given":"Ellen Paim","family":"de Abreu Paulo","sequence":"additional","affiliation":[{"name":"Laboratory of Development and Innovation, Butantan Institute, Sao Paulo 05585-000, Brazil"},{"name":"Faculty of Medicine, University of Sao Paulo (FMUSP), Sao Paulo 05508-220, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3747-255X","authenticated-orcid":false,"given":"Jean-Luc","family":"Poyet","sequence":"additional","affiliation":[{"name":"INSERM UMRS1342\u2014CNRS EMR8000, Institut De Recherche Saint-Louis, H\u00f4pital Saint-Louis, 75010 Paris, France"},{"name":"Universit\u00e9 Paris Cit\u00e9, 75006 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4120-8468","authenticated-orcid":false,"given":"Durvanei Augusto","family":"Maria","sequence":"additional","affiliation":[{"name":"Laboratory of Development and Innovation, Butantan Institute, Sao Paulo 05585-000, Brazil"},{"name":"Faculty of Medicine, University of Sao Paulo (FMUSP), Sao Paulo 05508-220, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bouaoud, J., Simon, C., Martinez, P., Gr\u00e9goire, V., Puppels, G.J., Bertolus, C., Breuskin, I., Koljenovi\u0107, S., Machiels, J.-P., and Elkabets, M. 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