As I've said, NF-kappaB triggers a lot of the bad genes in cancer. Here's another reason why EPA is probably a good anti-cancer agent if used correctly (at proper doses - too low = ineffective, too high - toxic to normal cells). Roger ------- J Am Coll Nutr. 2004 Feb;23(1):71-8. EPA Prevents LPS-Induced TNF-alpha Expression by Preventing NF-kappaB Activation. Zhao Y, Joshi-Barve S, Barve S, Chen LH. Graduate Center for Nutritional Sciences (Y.Z., L.H.C.), Internal Medicine (S.J.-B., S.B.), University of Kentucky, Lexington, KY. BACKGROUND: Many studies have shown that fish oil supplementation inhibits tumor necrosis factor- alpha (TNF-alpha) production in mice and human subjects; however, the mechanisms remain unclear. Nuclear factor-kappaB (NF-kappaB) is a transcription factor that plays an important role in controlling the expression of pro-inflammatory genes including TNF-alpha. Activation of NF-kappaB has been shown to mediate the maximal expression of TNF-alpha in human monocytes. NF-kappaB is kept in an inactive form in the cytoplasm by IkappaB, the inhibitory subunit of NF-kappaB complex. Phosphorylation and subsequent degradation of IkappaB lead to NF-kappaB activation. OBJECTIVES: The effect of eicosapentaenoic acid (EPA), a major n-3 fatty acid in fish oil, on the lipopolysaccharide (LPS)-induced expression of TNF-alpha and activation of NF-kappaB were investigated. The mechanism underlying EPA modulation of NF-kappaB activation was also studied. METHODS: Human monocytic THP-1 cells were pre-incubated with EPA and stimulated with LPS. The levels of secreted TNF-alpha were determined by ELISA. The DNA binding activity of NF-kappaB was analyzed by EMSA. The degradation and phosphorylation of IkappaB-alpha were examined by Western blot analysis. RESULTS: TNF-alpha production and expression induced by LPS were significantly decreased in cells pre-incubated with EPA. LPS-induced NF-kappaB activation, translocation of p65 subunit to the nucleus, phosphorylation and degradation of IkappaB-alpha were partially prevented by EPA. CONCLUSIONS: The results suggest that suppression of the TNF-alpha expression by EPA is partly attributed to its inhibitory effect on NF-kappaB activation. EPA appears to prevent NF-kappaB activation by preventing the phosphorylation of IkappaB-alpha.
