Antiproliferative and cytotoxic effects of sodium selenite in human colon cancer cells.
Sodium selenite has been reported to interfere with cell growth and proliferation and to induce cell death. Despite of our current knowledge, details about its effects on growth and behavior of colonocytes with differing p53 status remain unknown. In our study, we evaluated the antiproliferative, cell cycle specific and proapoptotic potential of sodium selenite in HCT-116 colorectal cells with wild type p53 and its isogenic control HCT-116-p53KO cell line. Cell proliferation in selenite-treated cells was followed by computer-enhanced time-lapse videomicroscopy, by measuring protein content (Coomassie Brilliant Blue assay), metabolic activity (WST-1) and DNA synthesis (BrdU). Changes in cell cycle were determined by flow cytometry and Western blotting. Cell death was measured with the nuclear fragmentation assay and caspase-3 immunostaining. We show that sodium selenite inhibits the growth and proliferation of colon cancer cells in a time- and dose-dependent manner, with HCT-116 cells being more sensitive than HCT-116-p53KO cells. Moreover, upon sodium selenite treatment, there was a tendency for cells to accumulate at G2 phase which was accompanied by the increasing expression of cyclin B1, Cdc2 p34, p21 and the sub G1 fraction of the cell cycle. In addition, PARP and nuclear fragmentation and activation of caspase-3 were more profound in HCT-116 cells versus HCT-116-p53KO cells, thus indicating important role of p53 and dependent signaling in selenite-induced toxicity.
Králová
Vera
V
Department of Medical Biology, Charles University, Faculty of Medicine in Hradec Kralove, Simkova 870, 500 38, Hradec Kralove, Czech Republic.
Brigulová
Katerina
K
Cervinka
Miroslav
M
Rudolf
Emil
E
D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis; D045325:HCT116 Cells; D006801:Humans; D018038:Sodium Selenite / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; D018038:Sodium Selenite