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

Abstract

PURPOSE:

Increasing evidence suggests that interaction between the chemoattractant CXCL12/stromal cell-derived factor-1alpha 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 (IC(50), 7.5 micro g/ml) but did not inhibit CCL2-, CCL3-, CCL5-, formylmethionylleucylphenylalanine (fMLP)-, or C5a-induced migration. The compound markedly blocked CXCL12 binding to THP-1 cells (IC(50), 0.36 micro g/ml). Tannic acid also inhibited CXCL12-induced, but not epidermal growth factor-induced, migration of MDA 231 breast tumor cells. Additionally, 0.5 micro g/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.

• Authors: Xin Chen, John A Beutler, Thomas G McCloud, Amy Loehfelm, Lu Yang, Hui-Fang Dong, Oleg Y Chertov, Rosalba Salcedo, Joost J Oppenheim, O M Zack Howard
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 9 Issue 8 Pg. 3115-23 (Aug 01 2003) ISSN: 1078-0432 [Print] United States
• PMID: 12912963 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Angiogenesis Inhibitors
• CXCL12 protein, human
• Chemokine CXCL12
• Chemokines, CXC
• Drugs, Chinese Herbal
• Hydrolyzable Tannins
• Ligands
• Plant Preparations
• Receptors, CXCR4
• Huang Qi

Topics

• Angiogenesis Inhibitors (therapeutic use)
• Animals
• Astragalus Plant
• Astragalus propinquus
• Capillaries (metabolism)
• Cattle
• Cell Division
• Cell Line
• Cell Line, Tumor
• Cell Movement
• Cell Separation
• Cells, Cultured
• Chemokine CXCL12
• Chemokines, CXC (antagonists & inhibitors)
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal (therapeutic use)
• Endothelium, Vascular (metabolism, pathology)
• Flow Cytometry
• Forsythia (metabolism)
• Humans
• Hydrolyzable Tannins (metabolism, therapeutic use)
• Inhibitory Concentration 50
• Ligands
• Lonicera
• Monocytes (drug effects, metabolism)
• Neovascularization, Pathologic
• Phytotherapy
• Plant Preparations (therapeutic use)
• Plant Structures
• Protein Binding
• Receptors, CXCR4 (antagonists & inhibitors)