ω-3 (right), but not ω-6 (left), fatty acids restore TGFβRII expression.
As colon carcinogenesis is accompanied by an increase in the expression of the lipid-dependent protein kinase CβII (PKCβII), the authors reasoned that ω-3 fatty acids might inhibit PKCβII signaling. Analysis of rat colonic epithelia and PKCβII transgenic mice demonstrated that ω-3 fatty acids block PKCβII activation and reduce the pro-carcinogenic effects of PKCβII in vitro and in vivo. PKCβII appears to repress the expression of transforming growth factor β receptor II (TGFβRII), desensitizing cells to the growth-inhibiting effects of TGFβ.
The results suggest that ω-3 fatty acids inhibit PKCβII, thus relieving the inhibition of TGFβRII expression. This renders colon epithelial cells sensitive to TGFβ, and prevents or reverses the hyperproliferative state that leads to colon cancer. Dietary ω-3 fatty acids are also associated with preventing prostate and breast cancer and some neurological conditions, suggesting that PKCβII may be a promising target for multiple chemoprevention strategies. ▪
