The Role of NF- [kappa] B in PPAR [alpha] -Mediated Hepatocarcinogenesis

In this review, the role of NF- κ B in the induction of hepatocarcinogenesis by peroxisome proliferators is examined. The administration of peroxisome proliferators for more than a three-day period leads to the activation of NF- κ B in the livers of rats and mice. On the other hand, peroxisome proliferator activated receptor- α (PPAR α ) activation in non-hepatic tissues can lead to the inhibition of NF- κ B activation. Several lines of evidence support the hypothesis that the activation of NF- κ B by peroxisome proliferators in the liver is mediated by oxidative stress. The role of NF- κ B in peroxisome proliferator-induced hepatocarcinogenesis has been examined using NF- κ B knockout models. Specifically, the induction of cell proliferation and the promotion of liver carcinogenesis are inhibited in mice lacking the p50 subunit of NF- κ B. Overall, the activation of NF- κ B appears to be important in the carcinogenic activity of peroxisome proliferators.