Tannic acid derivatives display anti-angiogenic properties in human breast cancer cells by interfering with CXCR4/SDF-1 interactions

5190

Angiogenesis involves the formation and stabilization of new blood vessels. Tumors rely on this process to meet their constantly increasing demands for nutrients and oxygen. Research has shown that stromal-cell derived factor-1_ (SDF-1_) is involved in angiogenesis by up regulating key angiogenic factors including vascular endothelial growth factor (VEGF), which in turn increases the cell membrane expression of CXCR4. Previous studies have shown that tannic acid inhibits the binding of SDF-1_ and CXCR4, decreasing the angiogenesis measured by the chicken choriallantoic membrane (CAM) assay. We hypothesize that 3 derivatives of tannic acid (ferulic acid, ellagic acid and gallic acid) will posses its same anti-angiogenic potential. Ferulic acid is a phenolic plant derived organic acid possessing antioxidant properties. It has also been demonstrated to boost the immune system and aide in the body’s protection against UV light. Gallic acid, a trihydroxybenzoic acid, is a natural antioxidant found in walnuts, tea leaves, oak bark and other plant extracts. Ellagic acid is a polyphenolic compound found in berries and known for its cancer fighting properties. In this study we use MDA-MB-231 and MDA-MB-435 (high CXCR4 expressing) and MCF-7 (low CXCR4 expressing) breast adenocarcinoma cell lines. Cells are placed on the CAM of fertilized chicken eggs at a concentration of 5 x 105 cells/20 _L with SDF-1_ (100 ng/mL), and derivative concentrations ranging from 5 _M to 25 _M. We then quantify angiogenesis using a novel analytical computer program, which measures blood vessel density, length, and branching points. Our controls were untreated eggs, eggs with the cancer cells only, and eggs with the cancer cells and SDF-1_. In this study we report optimal inhibition at a 5 _M concentration where tannic acid decreases blood vessel density by 65% (p ≤ 0.0244), blood vessel length by 71% (p≤ 0.000), and branching points by 70% (p≤ 0.000) in comparison to the SDF-1_ control in MDA-MB-435. Ferulic acid at the same concentration showed similar inhibition of angiogenesis, causing an 80% reduction in blood vessel density, a 48% reduction in branching points and a 70% decrease in blood vessel length. The other two derivatives show related trends in their anti-angiogenic capacity. MDA-MB-231 angiogenesis inhibition paralleled that of MDA-MB-435. On the other hand, the addition of tannic acid derivatives to MCF-7 showed little anti-angiogenic potential. We assume that this may be due to their low expression of CXCR4. Further research may be required to validate this hypothesis.