roger

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
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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 ****yzed by EMSA. The
degradation and phosphorylation of IkappaB-alpha were examined by Western
blot ****ysis.

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.