The anthocyanidins cyanidin and delphinidin are potent inhibitors of the epidermal growth-factor receptor

The aglycons of the most abundant anthocyanins in food, cyanidin (cy) and d elphinidin (del), were found to inhibit the growth of human tumor cells in vitro in the micromolar range, whereas malvidin (mv), a typical anthocyanid in in grapes, was less active. The aglycons preferentially inhibited the gr owth of the human vulva carcinoma cell line A431, overexpressing the epider mal growth-factor receptor (EGFR). The glycosides cyanidin-3-beta -D-galact oside (cy-3-gal, idaein) and malvidin-3-beta -D-glucoside (mv-3-glc, oenin) did not affect tumor cell growth up to 100 muM. The tyrosine kinase activi ty of the EG;FR, isolated from A431 cells, was potently inhibited by cy and del. My and the glycosides cy-3-gal and mv-3-glc were inactive up to 100 m uM. In intact cells the influence of anthocyanin treatment on downstream si gnaling cascades was investigated by measuring the phosphorylation of the t ranscription factor Elk-1. A431 cells were transiently transfected with a l uciferase reporter gene construct whose expression is controlled by MAP kin ase pathway dependent phosphorylation of a GAL4-Elk-1 fusion protein. We fo und that cy and del inhibited the activation of the GAL4-Elk-1 fusion prote in in the concentration range where growth inhibition was observed. Thus, t he anthocyanidins cy and del are potent inhibitors of the EGFR, shutting of f downstream signaling cascades. These effects might contribute substantial ly to the growth-inhibitory properties of these natural food constituents.