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Tannic acid is an inhibitor of CXCL12 (SDF-1 alpha)/CXCR4 with antiangiogenic activity

  1. Author:
    Chen, X.
    Beutler, J. A.
    McCloud, T. G.
    Loehfelm, A.
    Yang, L.
    Dong, H. F.
    Chertov, O. Y.
    Salcedo, R.
    Oppenheim, J. J.
    Howard, O. M. Z.

  2. Author Address

    Natl Canc Inst, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21702 USA Natl Canc Inst, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21702 USA Natl Canc Inst, Basic Res Program, Ctr Canc Res, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA Natl Canc Inst, Mol Targets Discovery Program, Ctr Canc Res, Frederick, MD 21702 USA TherImmune Res Corp, Gaithersburg, MD 20879 USA Howard OMZ Natl Canc Inst, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21702 USA
    1. Year: 2003
  2. Journal: Clinical Cancer Research
    1. 9
    2. 8
    3. Pages: 3115-3123
  4. Type of Article: Article
  1. Abstract:

    Purpose: Increasing evidence suggests that interaction between the chemoattractant CXCL12/stromal cell-derived factor-la and its receptor CXCR4 plays a pivotal role in the metastasis of various tumors. Our previous studies showed that multi- component Chinese herbal medicines inhibited the effects of CXCL12/CXCR4. As a result of sequential chromatographic fractionation of one herbal medicine ingredient, Lianqiao (fruit of Forsythia suspensa), we observed that tannins were, at least in part, responsible for this activity. The aim of this study was to assess the anti-CXCL12/CXCR4 activity of a commercial tannic acid and evaluate its potential to inhibit tumor cell migration and angiogenesis in vitro. Experimental Design: The inhibitory effect of tannic acid on CXCL12/CXCR4 was measured by chemotaxis assay, ligand binding assay, and fluorescence-activated cell sorter analysis. The antiangiogenic effect of tannic acid was assessed by in vitro endothelial cell tube formation. Results: Tannic acid, at nontoxic concentrations, specifically inhibited CXCL12-induced human monocyte migration (IC50, 7.5 mug/ml) but did not inhibit CCL2- , CCL3-, CCL5-, formylmethionylleucylphenylalanine (fMLP)-, or C5a-induced migration. The compound markedly blocked CXCL12 binding to THP-1 cells (IC50, 0.36 mug/ml). Tannic acid also inhibited CXCL12-induced, but not epidermal growth factor- induced, migration of MDA 231 breast tumor cells. Additionally, 0.5 mug/ml of tannic acid selectively inhibited CXCL12- mediated, but not basic fibroblast growth factor- or endothelial cell growth supplement-mediated, bovine aorta endothelial cell capillary tube formation. Conclusion: These studies indicate that tannic acid is a novel selective CXCL12/CXCR4 antagonist and consequently may provide a mechanistic basis for the reported antitumor and anti- inflammatory properties of tannic acid.

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