Selenium is critical for cancer-signaling gene expression but not cell proliferation in human colon Caco-2 cells.
Selenium (Se) is a potential anticarcinogenic nutrient, and the essential role of Se in cell growth is well recognized but certain cancer cells appear to have acquired a survival advantage under conditions of Se-deficiency. To understand the molecular basis of Se-anticancer effects at nutritional doses (nmol/L) for cultured cells, we generated Se-deficient colon Caco-2 cells by gradually reducing serum in media because serum contains a trace amount of Se. The glutathione peroxidase (GPx) activity of Se-deficient Caco-2 cells was 10.8 mU/mg protein compared to 133.6 approximately 146.3 mU/mg protein in Caco-2 cells supplemented with 500 nmol/L selenite, SeMSC or SeMet (three tested Se-chemical forms) after 7-d culture in serum free media. Interestingly, there were no detectable differences in cell growth, cell cycle progression between Se-deficient cells and cells supplemented with 500 nmol/L Se. To examine differential cancer signaling-gene expression between Se-deficient and Se-supplemented cells, we employed a cancer signal pathway-specific array assay coupled with the real time PCR analysis. Our data demonstrate that although Caco-2 cells are resistant to Se deprivation, Se may exert its anticancer property through increasing the expression of humoral defense gene (A2M) and tumor suppressor-related genes (IGFBP3, HHIP) while decreasing pro-inflammatory gene (CXC L9, HSPB2) expression.
Zeng
Huawei
H
United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202-9034, USA. huawei.zeng@ars.usda.gov
Botnen
James H
JH
D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005979:Glutathione Peroxidase / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018036:Selenium Compounds / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000235:genetics*; D018038:Sodium Selenite / Q000494:pharmacology
D002352:Carrier Proteins; D016895:Culture Media, Serum-Free; C117596:HHIP protein, human; D055551:HSP27 Heat-Shock Proteins; C442250:HSPB2 protein, human; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D008562:Membrane Glycoproteins; D018036:Selenium Compounds; D005979:Glutathione Peroxidase; D018038:Sodium Selenite