Angiogenesis, the formation of new blood vessels, is critical to tumour growth and inflammation1. The discovery of angiogenesis inhibitors disclosed effective therapeutic strategies. Dietary food compounds have received increasingly attention in disease prevention2. The fruit of tomato is rich in compounds with potential anti-angiogenic activity such as lycopene and cystine-knot miniproteins (TCMPs)3. Aim of this study was to characterize in vitro the mechanism of the anti-angiogenic activity of TCMPs and lycopene. Using human umbilical vein endothelial cells (HUVEC), we found that TCMPs inhibit by approximately 50% the increase in cell migration induced by VEGF-A and significantly decrease the nitric oxide (NO) formation. On the contrary, lycopene increased NO production in VEGF-A- treated HUVEC. Fruits from several tomato varieties were analyzed for their TCMPs content, observing variations in TCMPs levels particularly in fresh-market varieties. Moreover, we identified putative cystine-knot proteins in other Solanaceae species (i.e. .tobacco and eggplant). These findings suggest that TCMPs may be of pharmacological interest.
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