American University of Beirut, Lebanon.
Cancer Biol Ther. 2011 Jul 1;12(1):59-68. doi: 10.4161/cbt.12.1.15715.
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 kappa B (NF-ĸB) in inflammation and cancer, we investigated the effect of GT on NF-ĸB signaling in HT-29 and HCT-116 human colon cancer cells. DNA binding assays revealed significant suppression of tumor necrosis factor (TNF-α)-induced NFĸB activation which correlated with the inhibition of IĸBα phosphorylation and degradation. Sequentially, p65 nuclear translocation and DNA binding were inhibited. GT also down-regulated the expression of NFĸB-regulated inflammatory cytokines (IL-8, TNF-α, IL-1α) 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-α and IL-1α 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-ĸB activation.
没食子单宁（GT）是一种多酚水解单宁，其抗炎和抗癌活性的机制尚未完全阐明。已经证明，GT 调节的几种作用与干扰炎症介质有关。鉴于核因子 kappa B（NF-ĸB）在炎症和癌症中的核心作用，我们研究了 GT 对 HT-29 和 HCT-116 人结肠癌细胞中 NF-ĸB 信号转导的影响。DNA 结合实验显示，肿瘤坏死因子（TNF-α）诱导的 NFĸB 激活受到显著抑制，这与 IĸBα磷酸化和降解的抑制有关。随后，p65 核易位和 DNA 结合被抑制。GT 还下调了 NFĸB 调节的炎症细胞因子（IL-8、TNF-α、IL-1α）的表达，并导致细胞周期停滞和细胞在 G1 期前积累。在体内，GT（25mg/kg 体重）在肿瘤接种前或后腹腔内（i.p.）注射，显著降低了 NOD/SCID 小鼠中人结肠癌细胞异种移植物的体积。GT 处理的异种移植物的微血管密度（CD31）明显降低，以及 IL-6、TNF-α 和 IL-1α 的 mRNA 表达水平以及增殖（Ki-67）和血管生成（VEGFA）蛋白明显降低，这可能解释了 GT 在体内的抗肿瘤作用。总的来说，我们的结果表明，GT 的抗炎和抗肿瘤活性可能部分通过抑制 NF-ĸB 激活来介导。
