Antitumor and Antiangiogenic Effect of Tannic Acid in the Advanced Stage of Ehrlich Ascites Tumor in Mice

Ehrlich ascites tumor (EAT) is a rapidly growing, angiogenesis-dependent tumor characterized by high levels of vascular endothelial growth factor (VEGF). VEGF contributes to ascites formation, which supports tumor cell growth and the accumulation of tumor-associated macrophages (TAMs), primarily of the immunosuppressive M2 phenotype. M2 macrophages promote tumor progression by secreting angiogenic and immunomodulatory factors such as VEGF, matrix metalloproteinases (MMPs), and cyclooxygenase-2 (COX-2). This study investigated the effects of tannic acid (TA) on tumor growth and angiogenesis in EAT-bearing mice, focusing on TAM–tumor cell interactions. We evaluated ascites volume, cell counts, macrophage activity, peritoneal angiogenesis and blood vessel density, concentrations of VEGF, COX-2, and MMP-2/-9, blood biomarkers, and DNA damage using the comet assay. TA treatment significantly reduced tumor growth and angiogenesis by modulating TAM function. Specifically, TA inhibited VEGF, COX-2, and MMP-2/-9 expression, decreased M2 macrophage numbers, and enhanced the antitumor immune response, as shown by increased lymphocyte activation and favorable shifts in lymphocyte-to-monocyte (LMR) and neutrophil-to-lymphocyte (NLR) ratios. Additionally, TA induced DNA fragmentation in tumor and blood cells, indicating cytotoxicity and potential induction of apoptosis. These findings suggest that TA’s inhibition of TAMs may be a promising strategy for treating tumors and other angiogenesis-related conditions.