A gamma-tocopherol-rich mixture of tocopherols inhibits colon inflammation and carcinogenesis in azoxymethane and dextran sulfate sodium-treated mice

Cancer Prev Res (Phila). 2009 Feb;2(2):143-52. doi: 10.1158/1940-6207.CAPR-08-0099. Epub 2009 Jan 20.

Abstract

We investigated the effects of a gamma-tocopherol-rich mixture of tocopherols (gamma-TmT, containing 57% gamma-T, 24% delta-T, and 13% alpha-T) on colon carcinogenesis in azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice. In experiment 1, 6-week-old male CF-1 mice were given a dose of AOM (10 mg/kg body weight, i.p.), and 1 week later, 1.5% DSS in drinking water for 1 week. The mice were maintained on either a gamma-TmT (0.3%)-enriched or a standard AIN93M diet, starting 1 week before the AOM injection, until the termination of experiment. In the AOM/DSS-treated mice, dietary gamma-TmT treatment resulted in a significantly lower colon inflammation index (52% of the control) on day 7 and number of colon adenomas (9% of the control) on week 7. gamma-TmT treatment also resulted in higher apoptotic index in adenomas, lower prostaglandin E2, leukotriene B4, and nitrotyrosine levels in the colon, and lower prostaglandin E2, leukotriene B4, and 8-isoprostane levels in the plasma on week 7. Some of the decreases were observed even on day 7. In experiment 2 with AOM/DSS- treated mice sacrificed on week 21, dietary 0.17% or 0.3% gamma-TmT treatment, starting 1 week before the AOM injection, significantly inhibited adenocarcinoma and adenoma formation in the colon (to 17-33% of the control). Dietary 0.3% gamma-TmT that was initiated after DSS treatment also exhibited a similar inhibitory activity. The present study showed that gamma-TmT effectively inhibited colon carcinogenesis in AOM/DSS-treated mice, and the inhibition may be due to the apoptosis-inducing, anti-inflammatory, antioxidative, and reactive nitrogen species-trapping activities of tocopherols.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / chemically induced
  • Adenocarcinoma / pathology
  • Adenocarcinoma / prevention & control
  • Adenoma / chemically induced
  • Adenoma / pathology
  • Adenoma / prevention & control
  • Animals
  • Antioxidants / therapeutic use*
  • Apoptosis / drug effects
  • Azoxymethane / toxicity*
  • Carcinogens / toxicity
  • Cell Transformation, Neoplastic / drug effects*
  • Cocarcinogenesis
  • Colon / drug effects
  • Colon / metabolism
  • Colon / pathology
  • Colonic Neoplasms / chemically induced
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / prevention & control*
  • Dextran Sulfate / toxicity*
  • Dinoprost / analogs & derivatives
  • Dinoprost / blood
  • Dinoprostone / blood
  • Dose-Response Relationship, Drug
  • Inflammation / drug therapy*
  • Leukotriene B4 / blood
  • Male
  • Mice
  • Tyrosine / analogs & derivatives
  • Tyrosine / blood
  • gamma-Tocopherol / therapeutic use*

Substances

  • Antioxidants
  • Carcinogens
  • Leukotriene B4
  • 8-epi-prostaglandin F2alpha
  • 3-nitrotyrosine
  • Tyrosine
  • gamma-Tocopherol
  • Dextran Sulfate
  • Dinoprost
  • Dinoprostone
  • Azoxymethane