Selenite and selenomethionine promote HL-60 cell cycle progression.
The essential role of selenium (Se) in nutrition is well established. The elucidation of the mechanisms by which selenium regulates the cell cycle can lead to a better understanding of the nature of selenium's essentiality and its role in disease prevention. In this study, the effects of selenium deficiency or adequacy (0.25 micromol/L selenite or selenomethionine) on HL-60 cell cycle progression were examined in serum-free media. Selenium was critical for promotion of HL-60 cell growth. Cell-cycle analysis revealed that selenium deficiency caused a decrease in G1 phase cells that corresponded to an increase in G2 and sub-G1 phase cells. Gene array analysis suggested that c-Myc, cyclin C, proliferating cell nuclear antigen, cyclin-dependent kinase (cdk)1, cdk2, cdk4, cyclin B and cyclin D2 mRNA levels were lower in selenium-deficient cells than in the cells supplemented with 0.25 micromol/L selenomethionine. The decrease in the c-Myc mRNA level in selenium-deficient cells was confirmed by reverse transcription-polymerase chain reaction analysis. Furthermore, the phosphorylation state of total cellular protein was higher (57%) in selenium-supplemented cells than in selenium-deficient cells. Collectively, these results suggest a novel role for selenium at 0.25 micromol/L in up-regulation of the expression of numerous cell cycle-related genes and total cellular phosphorylated proteins in HL-60 cells in serum-free culture media. This leads to the promotion of cell cycle progression, particularly G2/M transition and/or the reduction of apoptosis, primarily in G1 cells. These observations may have additional implications for understanding the nature of selenium's essentiality.
Zeng
Huawei
H
U.S. Department of Agriculture, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202-9034, USA. hzeng@gfhnrc.ars.usda.gov
D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics; D056745:Cyclin C; D016213:Cyclins / Q000187:drug effects* / Q000235:genetics; D005434:Flow Cytometry; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D008967:Molecular Biology; D010766:Phosphorylation / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012645:Selenomethionine / Q000494:pharmacology*; D018038:Sodium Selenite / Q000494:pharmacology*
C503674:CCNC protein, human; D056745:Cyclin C; D016213:Cyclins; D012645:Selenomethionine; D018038:Sodium Selenite