Tomatine Displays Antitumor Potential in In Vitro Models of Metastatic Melanoma

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.

Chemical Characterisation and Antihypertensive Effects of Locular Gel and Serum of Lycopersicum esculentum L. var. “Camone” Tomato in Spontaneously Hypertensive Rats

“…Moreover, tomatoes are the main source of lycopene in the human diet. All these tomato components have demonstrated strong protective effects against cancer [16] and cardiovascular disease [17], ischemia/reperfusion damage [18], as well as strong antioxidant properties [19]. Besides the well-known healthy properties of red (mature) tomatoes, immature green tomatoes contain low levels of carotenoids and high levels of a different family of secondary metabolites, known as steroid glycoalkaloids, such as α-tomatine and dehydrotomatine [20].…”

Sustainable Valorization of Tomato By-Products to Obtain Bioactive Compounds: Their Potential in Inflammation and Cancer Management

“…Additionally, tomatine have been demonstrated to inhibit the growth of a large range of cancer cells, such as colon, breast, lung, prostate, among others. Further investigation is necessary since most of the mechanisms of action are still unknown [ 14 , 15 , 16 ].…”

Biomaterial-Assisted Regenerative Medicine

“…Matrigel is a complex protein mixture of mouse Engelbreth-Holm-Swarm tumor [32,154]. Matrigel is effective in invasion assays of cancer cells, such as Boyden chamber or transwell [155]. In addition, Matrigel is also useful for the evaluation of the morphology of cancer cells.…”