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: Qing Jiang, Ziying Jiang, Yava Jones Hall, Yumi Jang, Paul W Snyder, Carol Bain, Jianjie Huang, Amber Jannasch, Bruce Cooper, Yun Wang, Michelle Moreland
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 65 Pg. 1069-1077 (Dec 2013) ISSN: 1873-4596 [Electronic] United States
• PMID: 24013093 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Anticarcinogenic Agents
• Antioxidants
• gamma-Tocopherol
• Dextran Sulfate

Topics

• Animals
• Anticarcinogenic Agents (pharmacokinetics, pharmacology)
• Antioxidants (pharmacokinetics, pharmacology)
• Carcinogenesis (drug effects)
• Colitis (chemically induced, drug therapy, pathology)
• Colonic Neoplasms (chemically induced, immunology, prevention & control)
• Dextran Sulfate
• Disease Progression
• Male
• Mice, Inbred BALB C
• gamma-Tocopherol (pharmacokinetics, pharmacology)