Inhibitory effect of selenite on invasion of HT1080 tumor cells.
Selenium, an essential biological trace element, has been shown to reduce and prevent the incidence of cancer. Our previous studies have shown that selenite is involved in the chemoprevention of cancer and induction of apoptosis of cancer cells. In this study, we demonstrate that selenite also inhibits the invasion of tumor cells. Cancer cell invasion requires coordinated processes, such as changes in cell-cell and cell-matrix adhesion, degradation of the extracellular matrix, and cell migration. We found that selenite inhibited invasion of HT1080 human fibrosarcoma cells. Adhesion of HT1080 cells to the collagen matrix was also inhibited by treatment with selenite, but cell-cell interaction and cell motility were not affected by selenite. Moreover, selenite reduced expression of matrix metalloproteinase-2 and -9 and urokinase-type plasminogen activator, which are involved in matrix degradation, but increased a tissue inhibitor of metalloproteinase-1. This inhibitory effect of selenite on the protease expressions was mediated by the suppression of transcription factors, NF-kappaB and AP-1. However, selenate showed no remarkable effect on all the steps of cancer cell invasion.
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon 305-701, South Korea.
S O
SO
Yoon
M M
MM
Kim
A S
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Chung
D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009362:Neoplasm Metastasis / Q000517:prevention & control; D064586:Selenic Acid; D018036:Selenium Compounds / Q000494:pharmacology; D018038:Sodium Selenite / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D016326:Extracellular Matrix Proteins; D018036:Selenium Compounds; D019715:Tissue Inhibitor of Metalloproteinase-1; D018038:Sodium Selenite; D064586:Selenic Acid