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Suppression of the Kinase Activity of Receptor Tyrosine Kinases by Anthocyanin-Rich Mixtures Extracted from Bilberries and Grapes

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    Suppression of the Kinase Activity of Receptor Tyrosine Kinases by Anthocyanin-Rich Mixtures Extracted from Bilberries and Grapes
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    Institute of Applied Biosciences, Section of Food Toxicology, Universität Karlsruhe (TH), Adenauerring 20, 76131 Karlsruhe, Germany, Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, 76021 Karlsruhe, Germany, University of Heidelberg, Medical Faculty Mannheim, Centre for Biomedicine and Medical Technology, 68167 Mannheim, Germany, and Endocannabinoid Research and Cancer Biomarkers and Prevention Groups, Department of Cancer Studies and Molecular Medicine, University of Leicester, United Kingdom
    * To whom correspondence should be addressed. Phone: +49 (721) 608-2936. Fax: +49 (721) 608-7254. E-mail: [email protected]
    †Universität Karlsruhe (TH).
    ‡Institute of Toxicology and Genetics.
    §University of Heidelberg.
    ∥Endocannabinoid Research, University of Leicester.
    ⊥Cancer Biomarkers and Prevention Groups, University of Leicester.
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    Journal of Agricultural and Food Chemistry

    Cite this: J. Agric. Food Chem. 2009, 57, 8, 3094–3101
    Click to copy citationCitation copied!
    https://doi.org/10.1021/jf803094a
    Published March 26, 2009
    Copyright © 2009 American Chemical Society
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    Abstract

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    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 ≤12.9 μg/mL, with preferential inhibition of VEGFR-2 and EGFR (≤3.4 μg/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 ≥50 μg/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.

    Copyright © 2009 American Chemical Society

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    Journal of Agricultural and Food Chemistry

    Cite this: J. Agric. Food Chem. 2009, 57, 8, 3094–3101
    Click to copy citationCitation copied!
    https://doi.org/10.1021/jf803094a
    Published March 26, 2009
    Copyright © 2009 American Chemical Society
    Request reuse permissions

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