Delphinidin-3-O-glucoside inhibits angiogenesis via VEGFR2 downregulation and migration through actin disruption

Abstract

Excessive angiogenesis favours cancer development, allowing cancer invasion. Polyphenols are promising chemopreventive agents, although data gather so far in respect of anthocyanins, namely cyanidin-3-O-glucoside and delphinidin-3-O-glucoside (DG) and respective aglycones are scarce. The capability of these compounds to prevent tumour progression by inhibiting angiogenesis/cell migration/proliferation was studied in: (i) chicken embryo chorioallantoic membrane assay; (ii) MDA-MB-231/MCF-12A cells to study proliferation and vascular endothelial growth factor receptor-2 (VEGFR-2) expression and cytoskeleton dynamics; (iii) in vitro assay to evaluate gastrointestinal digestion. The studied compounds promoted alterations on actin re/disassembly to form protrusions/stress fibres, evidencing capability to disrupt actin cytoskeleton dynamics and inhibiting angiogenesis, at least in part, by VEGFR-2 downregulation, with DG presenting the higher effect. Anthocyanin evidenced selectivity towards cancer cells by eliciting cytotoxicity on MDA-MB-231 cells and having a slight effect on healthy cells. Thus, DG evidenced the most promising profile as dietary supplement to achieve the biological desired effects.