Organo-Magnesium Suppresses Inflammation-Associated Colon Carcinogenesis in Male Crj: CD-1 Mice

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-magnesium (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, 10 mg/kg body weight) and followed by a one-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 ppm 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) and inflammation. 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 mRNA expression of certain pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, interferon-γ, and inducible nitric oxide synthase in the lesion-free colorectal mucosa at week 4, but increased the Nrf2 mRNA 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.

http://carcin.oxfordjournals.org/content/early/2012/11/01/carcin.bgs348.abstract

Voir le bulletin