title: Gamma-tocopherol attenuates moderate but not severe colitis and suppresses moderate colitis-promoted colon tumorigenesis in mice.
abstract: Inflammation can promote colon cancer. Mechanistic studies indicate that γ-tocopherol (γT), a major form of vitamin E in diets, has anti-inflammatory and anticancer properties. Here we investigated the effectiveness of γT and a mixture of tocopherols against colitis and colitis-promoted colon tumorigenesis in male BALB/c mice. γT or mixed tocopherols (at 0.1% diet) did not show any effect on colon tumorigenesis induced by azoxymethane (AOM, 10mg/kg) with three cycles of dextran sodium sulfate (DSS at 1.5-2.5%). γT failed to exhibit protection of severe colitis caused by three cycles of DSS at 2.5%. In contrast, when AOM-initiated carcinogenesis was promoted by relatively mild colitis induced by one-cycle DSS (1.5%), γT, but not mixed tocopherols, suppressed total multiplicity of macroscopic adenomas (P=0.06) and large adenomatous polyps (>2mm(2), P<0.05) by 60 and 85%, respectively. γT also significantly decreased tumor multiplicity (>2mm(2)) induced by AOM with two cycles of 1.5% DSS even when dietary supplementation was started after AOM injection. Consistently, γT but not mixed tocopherols attenuated DSS (1.5%)-induced colon inflammation and damage as well as formation of atypical glandular hyperplasia. Mice supplemented with tocopherols had high fecal excretion of 13'-carboxychromanol, a long-chain vitamin E metabolite shown to have potent anti-inflammatory activities. Our study demonstrates that γT is able to alleviate moderate but not severe colitis and its promoted tumorigenesis, and indicates that inflammation severity should be considered in evaluating anticancer effectiveness of chemoprevention agents.
authors.affiliation: Department of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA. Electronic address: qjiang@purdue.edu.
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Department of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Ziying
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Comparative Pathology, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Yava Jones
authors.initials: YJ
authors.lastname: Hall
authors.affiliation: Department of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Jang
authors.affiliation: Department of Comparative Pathology, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Snyder
authors.affiliation: Department of Comparative Pathology, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Bain
authors.affiliation: Department of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Jianjie
authors.initials: J
authors.lastname: Huang
authors.affiliation: Metabolite Profiling Facility Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Amber
authors.initials: A
authors.lastname: Jannasch
authors.affiliation: Metabolite Profiling Facility Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Cooper
authors.affiliation: Department of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Moreland
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D000975:Antioxidants / Q000493:pharmacokinetics / Q000494:pharmacology; D063646:Carcinogenesis / Q000187:drug effects*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D016264:Dextran Sulfate; D018450:Disease Progression; D008297:Male; D008807:Mice, Inbred BALB C; D024504:gamma-Tocopherol / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D024504:gamma-Tocopherol; D016264:Dextran Sulfate
keywords: 13′-COOH; 13′-carboxychromanol; AGH; AOM; Carboxychromanol; Colitis; Colon cancer; DSS; Inflammation; Tocopherol; Vitamin E; atypical glandular hyperplasia; azoxymethane; dextran sodium sulfate; α, β, γ, or δ-tocopherol; α-T, β-T, γ-T, or δ-T