It has been proposed that eukaryotic nuclear transcripton factor nuclear factor kappa-B (NF-κB) and cyclooxygenase-2 (COX-2) are implicated in the pathogenesis of many human diseases including cancer. Arsenic has been widely used in medicine in Oriental countries. Recent studies have shown that arsenic trioxide (As2O3) could induce in vitro growth inhibition and apoptosis of malignant lymphocytes, and myeloma cells. However, the molecular mechanisms by which AS2O3 initiates cellular signaling toward cell death are still unclear. In the present study, the effects of As2O3 on NF-κB and COX-2 expression in HL-60 cells were investigated. As2O3 suppressed DNA-binding activity of NF-κB composed of p65/p50 heterodimer through preventing the degradation of IκB-α and the nuclear translocation of p65 subsequently as well as interrupting the binding of NF-κB with their consensus sequences. Inhibitory effect of As2O3 on NF-κB DNA activity was dependent upon intracellular glutathione (GSH) and H2O2 level, but not superoxide anion. Futhermore, we found that As2O3 also downregulated the expression of COX-2, which has NF-κB binding site on its promoter through repressing the NF-κB DNA-binding activity.
|Original language||English (US)|
|Number of pages||13|
|Journal||Journal of cellular biochemistry|
|State||Published - Mar 1 2005|
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology