Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 12/1/2003
Publication Date: 3/23/2004
Citation: Zeng, H., Botnen, J.H. 2004. Copper inhibition of selenite-induced cell cycle arrest appears to be extracellular. Journal of Federation of American Societies for Experimental Biology. 18:A914.
Technical Abstract: Previous studies have demonstrated that copper (15.7 uM) can inhibit selenite (12.6 uM)-induced cytotoxicity and apoptosis in HT-29 cells. However, the exact nature of the interactions between selenium and copper is not fully understood. This study examined the effect of copper on the cell cycle arrest induced by selenite or selenocystine. Both selenite and selenocystine effectively inhibited cell growth and cell cycle progression. Cell cycle analysis revealed that selenite (3 to 5 uM) decreased G1 phase cells corresponding to an increase in S and G2 phase cells, but 0.625 or 1.25 uM copper substantially inhibited selenite-induced cell cycle arrest. In contrast, selenocystine increased G1 phase cells that corresponding with a decrease in S and G2 phase cells. Interestingly, 0.625 or 1.25 uM copper did not inhibit selenocystine-induced cell cycle arrest. A cell free gel shift assay demonstrated that selenite suppressed the inhibitory effect of copper on SP-1 DNA binding. Although 5 uM selenite in culture media significantly increased the intracellular selenium content, 1.25 uM copper sulfate blocked this increase. Collectively, these data demonstrate that selenite and selenocystine cause cell cycle arrest via different mechanisms. The results also suggest that an extracellular interaction between copper and selenite may be the basis of antagonism between these compounds