EPA (fatty acid) prevents NF-kappaB activation

Discussion in 'Health and medical' started by Roger, Feb 16, 2004.

  1. Roger

    Roger Guest

    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).


    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.