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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Dietary Prevention of Obesity-related Disease Research » Research » Publications at this Location » Publication #215292
Title: Selenium is critical for cancer-signaling gene expression but not cell proliferation in human colon Caco-2 cells

Author
item Zeng, Huawei
item Botnen, James

Submitted to: American Association of Cancer Research Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 8/30/2007
Publication Date: 11/23/2007
Citation: Zeng, H., Botnen, J.H. 2007. Selenium is critical for cancer-signaling gene expression but not cell proliferation in human colon Caco-2 cells. In: American Association of Cancer Research Meeting, Advances in Colon Cancer Research, November 14-17, Cambridge, MA. p. A6.

Interpretive Summary:

Technical Abstract: Selenium (Se) is an essential nutrient, and there is increasing evidence for the efficacy of certain forms of selenium as cancer-chemopreventive compounds. The essential role of Se in growth of most mammalian cells is well recognized but certain cancer cells appear to have acquired a survival advantage under conditions of Se-deficiency, and little is known about the role of Se in these cancer cells. Serum in mammalian cell culture media contains trace amount of Se, which is sufficient to maintain cellular selenoprotein such as cellular glutathione peroxidase (c-GPx) expression. To understand molecular basis of Se-anticancer effect at cellular nutritional dose (nmol/L), we generated Se-deficient Caco-2 cells with a serum gradual reduction method in the present study. The c-GPx activity of Se-deficient Caco-2 cells was 10.8 mU/mg protein compared with high c-GPx (133.6~146.3 mU/mg protein) activity in Caco-2 cells supplemented with 500 nmol/L selenite, SeMSC or SeMet (three tested Se chemical forms) during 7- day serum free culture condition. Interestingly, there were not detectable differences on cell growth, cell cycle progression between Se-deficient cells and cells supplemented with 500 nmol/L Se in media. This observation suggests, for the first time, that Caco-2 colon cancer cells have acquired a survival advantage under Se-deficient culture condition. To examine differential cancer signaling-gene expression between Se-deficient and Se-supplemented cells, we employed cancer signal pathway-specific array assay as an initial screen. 30 cancer related genes were then chosen and their expression was determined by a real time PCR analysis. Cancer related gene alpha-2-macroglobulin (A2M), insulin-like growth factor binding protein 3 (IGFBP3), hedgehog interacting protein (HHIP) were up regulated but chemokine (C-X-C motif) ligand 9 (CXC L9) and heat shock 27kDa protein 2 (HSPB2) were down regulated by one or two tested Se chemical forms; in particular, all three tested Se chemical forms up-regulated putative tumor suppressor IGFBP-3 gene. Collectively, our data demonstrated that Se increased the expression of tumor suppressor-related genes (IGFBP3, HHIP) and decreased pro-inflammatory gene (CXC L9, HSPB2) expression at cellular nutritional Se dose, even though Caco-2 colon cells were resistant to Se deprivation.