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Inhibition of inducible nitric oxide synthase expression by inositol hexaphosphate in cultured human colon cancer cells exposed to proinflammatory agents

Małgorzata Kapral ,  Joanna M. Wawszczyk ,  Stanisław Sośnicki ,  Ludmiła Węglarz 

Department of Biochemistry, Medical University of Silesia, Jedności 8, Sosnowiec 41-200, Poland


Inflammatory bowel diseases (IBDs) are chronic inflammatory conditions associated with increased risk in developing to colorectal cancer. A number of mediators of inflammation, such as pro-inflammatory cytokines, prostaglandins and nitric oxide have been involved in carcinogenesis, especially in the promotion and progression stages. NO is synthesized from L-arginine by constitutively expressed endothelial and neuronal nitric oxide synthases (eNOS and nNOS, respectively) and an inducible NOS (iNOS) isoform expressed under inflammatory conditions. Therefore, selective inhibitors of iNOS could be considered to be good candidates as chemopreventive agents against colon cancer. One of the promising dietary phytochemicals with preventive and therapeutic potential is inositol hexaphosphate (IP6), which demonstrated anti-cancer and anti-inflammatory properties in in vivo and in vitro studies.

In this study the effect of IP6 on the mRNA expression of iNOS stimulated with bacterial lipopolysaccharides (Escherichia coli and Salmonella typhimurium) and IL-1β in intestinal cells Caco-2 for 3, 6 and 12 h was investigated. A transcription level of iNOS was performed on cells after treatment with 1 and 2.5 mM IP6 by the use real time QRT-PCR technique.

Caco-2 exposed to IP6 only revealed an increase in iNOS gene expression after 3 h, but longer exposition (12h) caused a significant reduction in the level of mRNA. Stimulation of cells with pro-inflammatory factors (LPS and IL-1β) resulted in an up-expression of iNOS mRNA at 3, 6 and 12h. IP6 enhanced E. coli LPS-stimulated transcription of this gene after 3 h. At a concentration of 1 mM it affected down-expression of iNOS in cells treated with IL-1β or endotoxin of Salmonella. A decrease in iNOS transcription by IP6 following the gene induction by proinflammatory agents in 6 and 12 h lasting cultures was also determined.

The findings of this study suggest that one of the anti-cancer and anti-inflammatory abilities of IP6 can be realized by suppressing the expression of gene encoding inducible nitric oxide synthase isoform at the transcriptional level.


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Related papers

Presentation: Poster at IX Multidyscyplinarna Konferencja Nauki o Leku, by Małgorzata Kapral
See On-line Journal of IX Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2014-03-10 11:51
Revised:   2014-05-02 10:56