Gallotannin inhibits NFĸB signaling and growth of human colon cancer xenografts.

Abstract

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.

• Authors: Racha Al-Halabi, Mirella Bou Chedid, Raghida Abou Merhi, Hiba El-Hajj, Hind Zahr, Regine Schneider-Stock, Ali Bazarbachi, Hala Gali-Muhtasib
• Journal: Cancer biology & therapy (Cancer Biol Ther) Vol. 12 Issue 1 Pg. 59-68 (Jul 01 2011) ISSN: 1555-8576 [Electronic] United States
• PMID: 21532339 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Cytokines
• Hydrolyzable Tannins
• Inflammation Mediators
• Interleukin-1alpha
• Interleukin-6
• NF-kappa B
• NF-kappa B p50 Subunit
• NFKB1 protein, human
• Platelet Endothelial Cell Adhesion Molecule-1
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• I-kappa B Kinase

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, pharmacology)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Colonic Neoplasms (drug therapy, metabolism, pathology)
• Cytokines (metabolism)
• Female
• G1 Phase (drug effects)
• Humans
• Hydrolyzable Tannins (administration & dosage, pharmacology)
• I-kappa B Kinase (drug effects, metabolism)
• Inflammation Mediators (metabolism)
• Injections, Intraperitoneal
• Interleukin-1alpha (genetics)
• Interleukin-6 (genetics)
• Mice
• Mice, Inbred NOD
• Microvessels (drug effects, metabolism)
• NF-kappa B (antagonists & inhibitors, metabolism)
• NF-kappa B p50 Subunit (antagonists & inhibitors, metabolism)
• Platelet Endothelial Cell Adhesion Molecule-1 (drug effects, metabolism)
• RNA, Messenger
• Signal Transduction (drug effects)
• Tumor Necrosis Factor-alpha (drug effects, genetics)
• Xenograft Model Antitumor Assays