title: 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.affiliation: American University of Beirut, Lebanon.
authors.forename: Racha
authors.initials: R
authors.lastname: Al-Halabi
authors.forename: Mirella
authors.initials: M
authors.lastname: Bou Chedid
authors.forename: Raghida
authors.initials: R
authors.lastname: Abou Merhi
authors.forename: Hiba
authors.initials: H
authors.lastname: El-Hajj
authors.forename: Hind
authors.initials: H
authors.lastname: Zahr
authors.forename: Regine
authors.initials: R
authors.lastname: Schneider-Stock
authors.forename: Ali
authors.initials: A
authors.lastname: Bazarbachi
authors.forename: Hala
authors.initials: H
authors.lastname: Gali-Muhtasib
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D047348:Hydrolyzable Tannins / Q000008:administration & dosage / Q000494:pharmacology*; D051550:I-kappa B Kinase / Q000187:drug effects / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007274:Injections, Intraperitoneal; D053582:Interleukin-1alpha / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016207:Cytokines; D047348:Hydrolyzable Tannins; D018836:Inflammation Mediators; D053582:Interleukin-1alpha; D015850:Interleukin-6; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D051550:I-kappa B Kinase