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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 #149800
Title: COPPER MAY INTERACT WITH SELENITE EXTRACELLULARLY IN CULTURED HT-29 CELLS

Author
item Zeng, Huawei
item Botnen, James

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/11/2003
Publication Date: 3/1/2004
Citation: Zeng, H. and Botnen, J.H. 2004. Copper may interact with selenite extracellularly in cultured HT-29 cells. Journal of Nutritional Biochemistry. 15:179-184.

Interpretive Summary: Selenium is known to have anticancer effects which have been demonstrated in cultured cells, laboratory animals and human studies. Selenium can either stimulate or inhibit cell growth, depending on the concentration and chemical form of selenium. At concentrations higher than nutritional requirements, selenium has anticancer effects. Over the years, numerous elements such as As, Cu, Zn, Cd, Hg, Sn, Pb, Ni, Co, Sb, Bi, Ag, Au, and Mo have been found to inhibit anticancer effects of selenium. Copper, an essential trace element for humans, is also known to have anticancer effect in laboratory animal. On the other hand, cupric sulfate is distributed widely in drinking water, soil, food or the environment, and is likely to increase the possibility of subchronic toxicity in humans. Antagonism between copper and selenium has been documented in animal studies. In the present study, the effect of interactions between Se compounds (3 ~ 5 mmol/L) and CuSO4 (0.625 ~1.25 mmol/L) on cell cycle progression was examined. The data provide a mechanistic basis for considering interactions between copper and selenium at concentrations that may be influenced by human nutrition and dietary supplementation. These findings will be useful information for scientists and health-care people investigating possible anticarcinagenic properties of selenium and copper.

Technical Abstract: Previous studies have demonstrated that copper (15.7 µmol/L) can inhibit selenite (12.6 µmol/L)-induced cytotoxicity and apoptosis in HT-29 cells. However, the exact nature of the interactions between selenium and copper is not fully understood. In this study, the effect of copper on the cell cycle arrest induced by selenite or seleno-cystine was examined. Both selenite and seleno-cystine were effective in inhibition of cell growth and cell cycle progression. Cell-cycle analysis revealed that selenite (3~5 µmol/L) caused a decrease in G1 phase cells that corresponded with an increase in S and G2 phase cells, and 0.625 or 1.25 µmol/L copper sufficiently inhibited selenite induced cell cycle arrest. In contrast, seleno-cystine caused an increase in G1 phase cells that corresponded with a decrease in S and G2 phase cells. Interestingly, 0.625 or 1.25 µmol/L copper did not inhibit seleno-cystine induced cell cycle arrest. In addition, cell free gel shift assay demonstrated that selenite suppressed the inhibitory effect of copper on SP-1 DNA binding. Furthermore, although 5 µmol/L selenite in culture media significantly increases the intracellular selenium content, 1.25 µmol/L copper sulfate blocks this increase of the intracellular selenium content. Collectively, these data demonstrate that selenite and seleno-cystine cause cell cycle arrest via distinct mechanisms, and provide a basis for antagonism between copper sulfate and selenite in an in vitro system.