Organomagnesium suppresses inflammation-associated colon carcinogenesis in male Crj: CD-1 mice

Carcinogenesis. 2013 Feb;34(2):361-9. doi: 10.1093/carcin/bgs348. Epub 2012 Nov 3.

Abstract

Magnesium (Mg) deficiency increases genomic instability and Mg intake has been reported to be inversely associated with a risk of colorectal cancer (CRC). This study was designed to determine whether organo-Mg in drinking water suppresses inflammation-associated colon carcinogenesis in mice. Male Crj: CD-1 mice were initiated with a single i.p. injection of azoxymethane (AOM, 10mg/kg body weight) and followed by a 1 week exposure to dextran sulfate sodium (DSS, 1.5%, w/v) in drinking water to induce colonic neoplasms. They were then given the drinking water containing 7, 35 or 175 p.p.m. organo-Mg for 13 weeks. The chemopreventive efficacy of organo-Mg was determined 16 weeks after the AOM exposure. Administration with organo-Mg at all doses caused a significant inhibition of CRC development (P < 0.01 and P < 0.001). Especially, the highest dose of organo-Mg significantly suppressed the occurrence of all the colonic pathological lesions (mucosal ulcer, dysplasia, adenoma and adenocarcinoma). Organo-Mg also significantly reduced the number of mitoses/anaphase bridging, as well as proliferation of CRC. Additionally, at week 4, organo-Mg lowered the messenger RNA expression of certain proinflammatory cytokines, such as interleukin-1β, interleukin-6, interferon-γ and inducible nitric oxide synthase in the lesion-free colorectal mucosa at week 4 but increased the Nrf-2 messenger RNA expression. Our findings that organo-Mg inhibits inflammation-related mouse colon carcinogenesis by modulating the proliferative activities and chromosomal instability of CRC and suppressing colonic inflammation may suggest potential use of organo-Mg for clinical chemoprevention trials of CRC in the inflamed colon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / chemically induced
  • Adenocarcinoma / immunology
  • Adenocarcinoma / prevention & control*
  • Adenoma / chemically induced
  • Adenoma / immunology
  • Adenoma / prevention & control*
  • Animals
  • Apoptosis / drug effects
  • Azoxymethane / toxicity
  • Blotting, Western
  • Carcinogens / toxicity
  • Cell Proliferation / drug effects
  • Cell Transformation, Neoplastic / drug effects*
  • Colitis / chemically induced
  • Colitis / immunology
  • Colitis / prevention & control*
  • Colonic Neoplasms / chemically induced
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / prevention & control*
  • Dextran Sulfate / toxicity
  • Humans
  • Immunoenzyme Techniques
  • Inflammation / chemically induced
  • Inflammation / immunology
  • Inflammation / prevention & control*
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Magnesium Compounds / pharmacology*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mitotic Index
  • Organometallic Compounds / pharmacology
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • Carcinogens
  • Interleukin-1beta
  • Interleukin-6
  • Magnesium Compounds
  • Organometallic Compounds
  • RNA, Messenger
  • Recombinant Proteins
  • interferon gamma-1b
  • Interferon-gamma
  • Dextran Sulfate
  • Azoxymethane