{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:45:47Z","timestamp":1791222347475,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T00:00:00Z","timestamp":1595462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health and University of Bari, Italy","award":["Ricerca Corrente 2018-2020 and Fondi di Ateneo"],"award-info":[{"award-number":["Ricerca Corrente 2018-2020 and Fondi di Ateneo"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>There is a growing interest in the cytotoxic effects of bioactive glycoalkaloids, such as \u03b1-tomatine on tumor cells. Here, for the first time, we determine the antitumor potential of tomatine, a mixture of \u03b1-tomatine and dehydrotomatine, in metastatic melanoma (MM) cell lines harboring different BRAF and MC1R variants. We performed cytotoxicity experiments and annexin-V\/propidium iodide staining to assess the apoptotic\/necrotic status of the cells. ER stress and autophagy markers were revealed by Western Blot, whereas antiangiogenic and vascular-disrupting effects were evaluated through a capillary tube formation assay on matrigel and by ELISA kit for VEGF release determination. Cell invasion was determined by a Boyden chamber matrigel assay. Tomatine reduced 50% of cell viability and induced a concentration-dependent increase of apoptotic cells in the range of 0.5\u20131 \u03bcM in terms of \u03b1-tomatine. The extent of apoptosis was more than two-fold higher in V600BRAF-D184H\/D184H MC1R cells than in BRAF wild-type cells and V600BRAF-MC1R wild-type cell lines. Additionally, tomatine increased the LC3I\/II autophagy marker, p-eIF2\u03b1, and p-Erk1\/2 levels in BRAF wild-type cells. Notably, tomatine strongly reduced cell invasion and melanoma-dependent angiogenesis by reducing VEGF release and tumor-stimulating effects on capillary tube formation. Collectively, our findings support tomatine as a potential antitumor agent in MM.<\/jats:p>","DOI":"10.3390\/ijms21155243","type":"journal-article","created":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T09:06:09Z","timestamp":1595581569000},"page":"5243","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Tomatine Displays Antitumor Potential in In Vitro Models of Metastatic Melanoma"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4015-5205","authenticated-orcid":false,"given":"Simona","family":"Serrat\u00ec","sequence":"first","affiliation":[{"name":"Experimental Pharmacology Laboratory, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letizia","family":"Porcelli","sequence":"additional","affiliation":[{"name":"Experimental Pharmacology Laboratory, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8221-6694","authenticated-orcid":false,"given":"Stefania","family":"Guida","sequence":"additional","affiliation":[{"name":"Dermatology Unit, University of Modena and Reggio Emilia, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2279-9557","authenticated-orcid":false,"given":"Anna","family":"Ferretta","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences Neurosciences and Sense Organs, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Maria","family":"Iacobazzi","sequence":"additional","affiliation":[{"name":"Experimental Pharmacology Laboratory, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7171-3460","authenticated-orcid":false,"given":"Tiziana","family":"Cocco","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences Neurosciences and Sense Organs, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Immacolata","family":"Maida","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences Neurosciences and Sense Organs, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6796-8863","authenticated-orcid":false,"given":"Gabriella","family":"Tamasi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Chemistry and Pharmacology, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Chemistry and Pharmacology, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8219-0252","authenticated-orcid":false,"given":"Michele","family":"Manganelli","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences Neurosciences and Sense Organs, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Tommasi","sequence":"additional","affiliation":[{"name":"Molecular Diagnostics and Pharmacogenetics Unit, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia","family":"Azzariti","sequence":"additional","affiliation":[{"name":"Experimental Pharmacology Laboratory, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Guida","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences Neurosciences and Sense Organs, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2710","DOI":"10.1016\/j.bbamcr.2016.08.007","article-title":"New insight into the role of metabolic reprogramming in melanoma cells harboring BRAF mutations","volume":"1863","author":"Ferretta","year":"2016","journal-title":"Biochim. 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