| Abstract
| - The aglycons of the most abundant anthocyanins in food, cyanidin (cy) and delphinidin (del), werefound 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 thegrowth of the human vulva carcinoma cell line A431, overexpressing the epidermal growth-factorreceptor (EGFR). The glycosides cyanidin-3-β-d-galactoside (cy-3-gal, idaein) and malvidin-3-β-d-glucoside (mv-3-glc, oenin) did not affect tumor cell growth up to 100 μM. The tyrosine kinase activityof the EGFR, isolated from A431 cells, was potently inhibited by cy and del. Mv and the glycosidescy-3-gal and mv-3-glc were inactive up to 100 μM. In intact cells the influence of anthocyanintreatment on downstream signaling cascades was investigated by measuring the phosphorylationof the transcription factor Elk-1. A431 cells were transiently transfected with a luciferase reportergene construct whose expression is controlled by MAP kinase pathway dependent phosphorylationof 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, theanthocyanidins cy and del are potent inhibitors of the EGFR, shutting off downstream signalingcascades. These effects might contribute substantially to the growth-inhibitory properties of thesenatural food constituents. Keywords: Anthocyanins; cyanidin; delphinidin; malvidin; idaein; oenin; sulforhodamine B assay;EGFR; Elk-1
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