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Research Paper
Selenomethionine Regulates Cyclooxygenase-2 (COX-2) Expression Through Nuclear Factor-Kappa B (NF-kB) in Colon Cancer Cells
Durga P Cherukuri, Anne-Christine Goulet, Hiroyasu Inoue, and Mark A Nelson
volume 4 | issue 2
February 2005Pages: 175-180
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Previously, we showed that selenomethionine (Se-Met) inhibits growth of colon cancer cells via suppressing COX-2 expression at both mRNA and protein level. However, the molecular mechanism by which Se-Met suppresses COX-2 expression remains to be elucidated. To this end, we transiently transfected HCA7 cells with different COX-2 promoter constructs followed by Se-Met treatment (90 µM) for 12 h. The results suggested the role of nuclear factor-kappa B (NF-kB) in transcriptional regulation of COX-2. We also observed complete inhibition of DNA binding activity of NF-kB in Se-Met (90 µM) treated HCA7 cells as shown by electrophoretic mobility shift assay (EMSA). Supershift assays with anti-p65 antibody identified p65 subunit in the protein complex. We further demonstrate dose-dependent inhibition of nuclear translocation of NF-kB/p65 in Se-Met treated HCA7 cells, which could explain the observed reduction in DNA binding of NF-kB/p65. These results suggest that Se-Met regulates COX-2 at transcriptional level by modulating the activity of NF-kB transcription factor.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.