Tomatine Displays Antitumor Potential in In Vitro Models of Metastatic Melanoma
Autor: | 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 |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: | |
Zdroj: | International Journal of Molecular Sciences, Vol 21, Iss 15, p 5243 (2020) |
Druh dokumentu: | article |
ISSN: | 1422-0067 1661-6596 |
DOI: | 10.3390/ijms21155243 |
Popis: | 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. |
Databáze: | Directory of Open Access Journals |
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