Rottlerin Inhibits ROS Formation and Prevents NF kappa B Activation in MCF-7 and HT-29 Cells
Rottlerin, a polyphenol isolated from Mallotus Philippinensis, has been recently used as a selective inhibitor of PKC delta, although it can inhibit many kinases and has several biological effects. Among them, we recently found that Rottlerin inhibits the Nuclear Factor kappa B (NF kappa B), activated by either phorbol esters or H2O2. Because of the redox sensitivity of NF kappa B and on the basis of Rottlerin antioxidant property, we hypothesized that Rottlerin could prevent NF kappa B activation acting as a free radicals scavenger, as other natural polyphenols. The current study confirms the antioxidant property of Rottlerin against the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) in vitro and against oxidative stress induced by H2O2 and by menadione in culture cells. We also demonstrate that Rottlerin prevents TNF alpha-dependent NF kappa B activation in MCF-7 cells and in HT-29 cells transfected with the NF kappa B-driven plasmid pBIIX-LUC, suggesting that Rottlerin can inhibit NF kappa B via several pathways and in several cell types.