{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:04:44Z","timestamp":1760058284406,"version":"build-2065373602"},"reference-count":67,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Research on viper venom has expanded into diverse medical applications, including cancer treatment. This study investigates the potential of Vipera ammodytes venom in oncology, evaluating its cytotoxicity and chemosensitising effects on malignant melanoma cells. Proteomic analysis identified 125 proteins in the venom, with Phospholipases A2, C-type lectins, and metalloproteinases among the most abundant components. These proteins are associated with cytotoxic, anti-proliferative, and tumor-inhibiting properties. Three melanoma cell lines (M001, Me501, and A375) were used to assess venom cytotoxicity. The IC50 values demonstrated consistent venom sensitivity across cell lines (approximately 1.1 \u00b5g\/mL). Combined treatment with venom and cisplatin significantly increased the cytotoxicity compared to single-agent treatments. Notably, venom enhanced the sensitivity of cisplatin in resistant cell lines (M001 and Me501), increasing cell mortality by up to 40%. The A375 cell line, inherently more sensitive to cisplatin, exhibited additional cytotoxic effects only at higher venom doses. The morphological changes observed under microscopy confirmed venom-induced cellular changes, further supporting its potential as an anti-cancer agent. The selective targeting of melanoma cells by venom components, particularly in muscle-associated metastases, suggests a unique therapeutic niche. While cisplatin was chosen for this pilot study due to its established cytotoxicity, future research will explore venom combinations with contemporary treatments such as immunotherapy and targeted therapies. Although preliminary, these findings provide a foundation for integrating venom-based strategies into advanced melanoma protocols, aiming to improve outcomes in resistant or metastatic cases.<\/jats:p>","DOI":"10.3390\/toxins17040152","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T04:48:18Z","timestamp":1742791698000},"page":"152","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhancing the Efficacy of Melanoma Treatment: The In Vitro Chemosensitising Impact of Vipera ammodytes Venom on Human Melanoma Cell Lines"],"prefix":"10.3390","volume":"17","author":[{"given":"Giovanni","family":"Paolino","sequence":"first","affiliation":[{"name":"Unit of Dermatology and Cosmetology, IRCCS San Raffaele Hospital, Via Olgettina 60, 20132 Milan, Italy"},{"name":"Faculty of Medicine and Surgery, Universit\u00e0 Vita-Salute San Raffaele, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7199-0804","authenticated-orcid":false,"given":"Matteo Riccardo","family":"Di Nicola","sequence":"additional","affiliation":[{"name":"Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d\u2019Aosta, Via Bologna 148, 10154 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Raggi","sequence":"additional","affiliation":[{"name":"Department of Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serena","family":"Camerini","sequence":"additional","affiliation":[{"name":"Core Facilities, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0245-6709","authenticated-orcid":false,"given":"Marialuisa","family":"Casella","sequence":"additional","affiliation":[{"name":"Core Facilities, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3484-6288","authenticated-orcid":false,"given":"Luca","family":"Pasquini","sequence":"additional","affiliation":[{"name":"Core Facilities, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5530-0893","authenticated-orcid":false,"given":"Cristiana","family":"Zanetti","sequence":"additional","affiliation":[{"name":"Department of Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Russo","sequence":"additional","affiliation":[{"name":"Unit of Immuno-Biotherapy of Melanoma and Solid Tumors, IRCCS San Raffaele Hospital, Via Olgettina 60, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santo Raffaele","family":"Mercuri","sequence":"additional","affiliation":[{"name":"Unit of Dermatology and Cosmetology, IRCCS San Raffaele Hospital, Via Olgettina 60, 20132 Milan, Italy"},{"name":"Faculty of Medicine and Surgery, Universit\u00e0 Vita-Salute San Raffaele, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8778-2601","authenticated-orcid":false,"given":"Luana","family":"Lugini","sequence":"additional","affiliation":[{"name":"Department of Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6366-0231","authenticated-orcid":false,"given":"Cristina","family":"Federici","sequence":"additional","affiliation":[{"name":"Department of Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hempel, B.-F., Damm, M., G\u00f6\u00e7men, B., Karis, M., Oguz, M., Nalbantsoy, A., and S\u00fcssmuth, R. 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