Two standardized
anthocyanin-rich mixtures were investigated for their ability to inhibit the
receptor tyrosine kinases (RTKs) EGFR, ErbB2, ErbB3,
VEGFR-2, and
VEGFR-3. Both mixtures reduced the
kinase activity of recombinant
kinase domains of each RTK at concentrations <or=12.9 microg/mL, with preferential inhibition of
VEGFR-2 and EGFR (<or=3.4 microg/mL). Similarly,
ligand-induced autophosphorylation of these RTKs in human vulva
carcinoma or porcine aortic endothelial cells was suppressed by both mixtures, with ErbB3 and
VEGFR-3 being preferentially inhibited.
Anthocyanin-rich extracts completely abrogated
VEGFR-3 phosphorylation at concentrations of >or=50 microg/mL. These results indicate that
anthocyanin-rich mixtures can inhibit RTKs with low specificity. The rank order of inhibitory efficacy against the tested RTKs in intact cells was
VEGFR-3 >>
VEGFR-2 > ErbB3 > EGFR > ErbB2. Considering the important role of RTKs in
carcinogenesis, their inhibition by
anthocyanin-rich mixtures suggests that they may serve as
biomarkers of the pharmacological efficacy of
anthocyanins in future
chemoprevention experiments and in clinical intervention studies.