NFκB: A Promising Target for Natural Products in Cancer Chemoprevention

The transcription factor nuclear factor kappa B (NF kappa B) is found in nearly all animal cell types. It is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL and microbial antigens, and has been shown to regulate the expression of a number of genes including bcl-2, bcl-xl, cIAP, suvivin, TRAF, COX-2, MMP-9, iNOS and cell cycle-regulatory components. Many carcinogens, inflammatory agents and tumor promoters have been shown to activate NF kappa B, and resulting tumors demonstrate misregulated NF kappa B. Incorrect regulation of NF kappa B has been linked to inflammatory and autoimmune diseases, septic shock, viral infection and improper immune development. Aberrant regulation of NF kappa B is involved in cancer development and progression as well as in drug resistance. Inhibitors of NF kappa B mediate effects potentially leading to antitumor responses or greater sensitivity to the action of antitumor agents. Tools have been developed for the rapid assessment of NF kappa B activity, so in concert with a better understanding of NF kappa B activation mechanisms, many agents capable of suppressing NF kappa B activation have been identified. The present article focuses on the functions of NF kappa B, its role in human cancer and the therapeutic potential and benefit of targeting NF kappa B by natural products in cancer chemoprevention. Copyright (C) 2010 John Wiley & Sons, Ltd.