Selenomethionine regulates cyclooxygenase-2 (COX-2) expression through nuclear factor-kappa B (NF-kB) in colon cancer cells

Abstract

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.