NFkappaB: a promising target for natural products in cancer chemoprevention.

The transcription factor nuclear factor kappa B (NFkappaB) 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 NFkappaB, and resulting tumors demonstrate misregulated NFkappaB. Incorrect regulation of NFkappaB has been linked to inflammatory and autoimmune diseases, septic shock, viral infection and improper immune development. Aberrant regulation of NFkappaB is involved in cancer development and progression as well as in drug resistance. Inhibitors of NFkappaB 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 NFkappaB activity, so in concert with a better understanding of NFkappaB activation mechanisms, many agents capable of suppressing NFkappaB activation have been identified. The present article focuses on the functions of NFkappaB, its role in human cancer and the therapeutic potential and benefit of targeting NFkappaB by natural products in cancer chemoprevention.