Gallotannin inhibits NFκB signaling and growth of human colon cancer xenografts

Gallotannin (GT), the polyphenolic hydrolyzable tannin, exhibits anti-inflammatory and anticancer activities through mechanisms that are not fully understood. Several effects modulated by GT have been shown to be linked to interference with inflammatory mediators. Considering the central role of nuclear factor kappaB (NF kappa B) in inflammation and cancer, we investigated the effect of GT on NF kappa B signaling in HT-29 and HCT-116 human colon cancer cells. DNA binding assays revealed significant suppression of tumor necrosis factor (TNF alpha)-induced NF kappa B activation which correlated with the inhibition of I kappa B alpha phosphorylation and degradation. Sequentially, p65 nuclear translocation and DNA binding were inhibited. GT also downregulated the expression of NF kappa B-regulated inflammatory cytokines (IL-8, TNF alpha, IL-1 alpha) and caused cell cycle arrest and accumulation of cells in pre-G(1) phase. In vivo, GT (25 mg/kg body weight) injected intraperitoneally (i.p.) prior to or after tumor inoculation significantly decreased the volume of human colon cancer xenografts in NOD/SCID mice. GT-treated xenografts showed significantly lower microvessel density (CD31) as well as lower mRNA expression levels of IL-6, TNF alpha and IL-1 alpha and of the proliferation (Ki-67) and angiogenesis (VEGFA) proteins, which may explain GTs in vivo anti-tumorigenic effects. Overall, our results indicate that the anti-inflammatory and antitumor activities of GT may be mediated in part through the suppression of NF kappa B activation.