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Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 1/2/2002 Publication Date: 4/1/2002 Citation: Zeng, H. 2002. Selenite and selenomethionine promote HL-60 cell cycle progression. Journal of Nutrition. 132:674-679. Interpretive Summary: The essential nutritional role of selenium (Se) in animals and humans is well established. Trace amounts of selenium are found in human serum and are recognized as physiological concentrations. In contrast, at concentrations that are higher than physiological requirements, selenium can induce the cell death signaling pathway which is the main mechanism to inhibit cancer cell growth. It has been known that selenium at physiological concentrations is critical for the immune function, cell growth, and anti-cancer effects. The study of the effects of selenium on cell growth is important because cell growth is the most fundamental process of life, an understanding of which could uncover the mechanism of the anti-cancer effects of selenium. The effects of selenium at physiological concentrations on the promotion of cell growth were determined by studying human cells in culture. The current data suggest that selenium is critical for human lymphocyte cell division, growth and prevention of cell death. Numerous key cell growth related genes are responsible for the observed effects because selenium is likely to up regulate or stimulate the beneficial action of these genes. These findings will be useful for scientists and health-care professionals who are studying selenium status and human immune functions as well as policy makers who make recommendations for dietary intake of nutrients to promote health and well being. Technical Abstract: The essential role of selenium (Se) in animal and human nutrition is well established. Cancer and many human diseases are cell cycle diseases, the elucidation of the mechanisms by which Se regulates the cell cycle can lead to a better understanding of the nature of Se-essentiality and disease- prevention. In this study, the effects of either selenite or seleno- methionine (0.25uM, physiological concentration) on HL-60 cell cycle progression were examined in a serum-free media. 0.25 uM sodium selenite (Na**2SeO**3) and 0.25uM seleno-methionine were equally effective and critical in cell segregation, morphology and promotion of cell cycle progression/growth. Cell-cycle analysis revealed that, in the absence of sodium selenite (Na**2SeO**3) or seleno-methionine, there was a decrease in G1 phase cells that corresponded with an increase in G2 phase cells. This finding suggests that Se-deficiency, but not Se-adequacy, causes G2/M cell arrest and prevents G2 cells from segregating and entering mitosis. Relative cell cycle-related gene mRNA abundance determined by DNA array analysis suggested that c-Myc, cyclin C, PCNA, cdk1, cdk2, cdk4, cyclin B and cyclin D2 mRNA levels were higher in the cells supplemented with 0.25uM seleno-methionine than that of Se-deficient cells. The increase of c-Myc mRNA level in Se-supplemented cells was confirmed by RT-PCR assay. Furthermore, total cellular kinase protein (57%) was higher in Se- supplemented cells than that of Se-deficient cells. Collectively, these results suggest a novel role for selenite/seleno-methionine at physiological concentration (0.25uM) in up regulation of numerous cell cycle related gene expression and total cellular kinase protein, which are critical in cell cycle progression particularly in G2/M transition. |
