Tomatine Displays Antitumor Potential in In Vitro Models of Metastatic Melanoma.

Simona Serratì, Letizia Porcelli, Stefania Guida, Anna Ferretta, Rosa Maria Iacobazzi, Tiziana Cocco, Immacolata Maida, Gabriella Tamasi, Claudio Rossi, Michele Manganelli, Stefania Tommasi, Amalia Azzariti, Gabriella Guida

Research output: Contribution to journalArticlepeer-review

Abstract

There is a growing interest in the cytotoxic effects of bioactive glycoalkaloids, such as α-tomatine on tumor cells. Here, for the first time, we determine the antitumor potential of tomatine, a mixture of α-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 0.5-1 μM in terms of α-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-eIF2α, 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.

Original languageEnglish
Article number5243
JournalInternational Journal of Molecular Sciences
Volume21
Issue number15
DOIs
Publication statusPublished - Jul 23 2020

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