The aglycons of the most abundant
anthocyanins in food,
cyanidin (cy) and
delphinidin (del), were found to inhibit the growth of human
tumor cells in vitro in the micromolar range, whereas
malvidin (mv), a typical
anthocyanidin in grapes, was less active. The aglycons preferentially inhibited the growth of the human vulva
carcinoma cell line A431, overexpressing the
epidermal growth-factor receptor (EGFR). The
glycosides cyanidin-3-beta-D-galactoside (cy-3-gal, idaein) and malvidin-3-beta-D-glucoside (mv-3-glc, oenin) did not affect
tumor cell growth up to 100 microM. The
tyrosine kinase activity of the EGFR, isolated from A431 cells, was potently inhibited by cy and del. Mv and the
glycosides cy-3-gal and mv-3-glc were inactive up to 100 microM. In intact cells the influence of
anthocyanin treatment on downstream signaling cascades was investigated by measuring the phosphorylation of the
transcription factor Elk-1. A431 cells were transiently transfected with a
luciferase reporter gene construct whose expression is controlled by MAP
kinase pathway dependent phosphorylation of a GAL4-Elk-1 fusion
protein. We found that cy and del inhibited the activation of the GAL4-Elk-1 fusion
protein in the concentration range where growth inhibition was observed. Thus, the
anthocyanidins cy and del are potent inhibitors of the EGFR, shutting off downstream signaling cascades. These effects might contribute substantially to the growth-inhibitory properties of these natural food constituents.