Copper may interact with selenite extracellularly in cultured HT-29 cells

Previous studies have demonstrated that copper (15.7 mumol/L) can inhibit selenite (12.6 mumol/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 selenocystine was examined. Both selenite and selenocystine were effective in inhibition of cell growth and cell cycle progression. Cell cycle analysis revealed that selenite (3-5 mumol/L) caused a decrease in GI phase cells that corresponded with an increase in S and G2 phase cells, and that 0.625 or 1.25 mumol/L copper sufficiently inhibited selenite-induced cell cycle arrest. In contrast, selenocystine caused an increase in GI phase cells that corresponded with a decrease in S and G2 phase cells. Interestingly, 0.625 or 1.25 mumoUL copper did not inhibit selenocystine-induced cell cycle arrest. In addition, cell free get shift assay demonstrated that selenite suppressed the inhibitory effect of copper on SP-1 DNA binding. Furthermore, although 5 mumol/L selenite in culture media significantly increased the intracellular selenium content, 1.25 mumol/L copper sulfate blocked this increase of the intracellular selenium content. Collectively, these data demonstrate that selenite and selenocystine cause cell cycle arrest via distinct mechanisms, and suggest that copper may interact with selenite extracellularly, which represents the basis of antagonism between copper sulfate and selenite. Published by Elsevier Inc. All rights reserved.