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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 #236054

Title: Selenium as an Essential Micronutrient: Roles in Cell Cycle and Apoptosis

item Zeng, Huawei

Submitted to: Molecules
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/20/2009
Publication Date: 3/23/2009
Citation: Zeng, H. 2009. Selenium as an Essential Micronutrient: Roles in Cell Cycle and Apoptosis. Molecules. 14(3):1263-1278.

Interpretive Summary: Selenium is an essential trace element for humans and animals, and Se deficiency is associated with several disease conditions such as the immune impairment. In addition, selenium intakes that are greater than the recommended daily allowance (RDA) appear to protect against certain types of cancers. In humans and animals, cell proliferation and death must be regulated to maintain tissue homeostasis, and it has been well documented that the control of cell cycle progression and apoptosis is directly related to numerous human diseases. Thus, the elucidation of the mechanisms by which selenium regulates the cell cycle and apoptosis can lead to a better understanding of the nature of selenium’s essentiality and its role in disease prevention. This article reviews the status of knowledge concerning the effect of selenium on cell cycle and apoptosis. The information will be useful information for scientists and health-care professionals who are interested in nutrition and cancer prevention.

Technical Abstract: Selenium (Se) is an anticancer nutrient, and 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. The objective of the present study is to understand the molecular basis of Se-anticancer effects at a cellular nutritional dose (nmol/L). We generated Se-deficient colon Caco-2 cells by gradually reducing serum in the media because serum contains a trace amount of Se, which is sufficient to maintain the expression of cellular selenoproteins such as glutathione peroxidase (GPx). The GPx activity of Se-deficient Caco-2 cells was 10.8 mU/mg protein compared to 133.6~146.3 mU/mg protein in Caco-2 cells supplemented with 500 nmol/L selenite, se-(methyl)selenocysteine or selenomethionine (three tested Se chemical forms) after 7-day culture in serum free media. Interestingly, there were no detectable differences on cell growth, cell cycle progression between Se-deficient cells and cells supplemented with 500 nmol/L Se. This observation demonstrates, for the first time, that colon Caco-2 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 a cancer signal pathway-specific array assay coupled with the real time PCR analysis. Our data suggest that Se up-regulates the expression of humoral defense gene (A2M) and tumor suppressor-related genes (IGFBP3, HHIP) and but down-regulates pro-inflammatory gene (CXC L9, HSPB2) expression at cellular nutritional Se doses, even though colon Caco-2 cells were resistant to Se deprivation, and the change of IGFBP3 mRNA level occurs in human colon tumor tissues.