Abstract. Nuclear factor κB (NF-κB), a transcription factor, plays an important role in carcinogenesis as well as in the regulation of immune and inflammatory responses. NF-κB induces the expression of diverse target genes that promote cell proliferation, regulate apoptosis, facilitate angiogenesis and stimulate invasion and metastasis. Furthermore, many cancer cells show aberrant or constitutive NF-κB activation which mediates resistance to chemo-and radio-therapy. Therefore, the inhibition of NF-κB activation and its signaling pathway offers a potential cancer therapy strategy. In addition, recent studies have shown that NF-κB can also play a tumor suppressor role in certain settings. In this review, we focus on the role of NF-κB in carcinogenesis and the therapeutic potential of targeting NF-κB in cancer therapy.Keywords: NF-κB, NF-κB inhibitor, carcinogenesis, cancer therapy Structure, function and regulation of NF-κBNuclear factor-κB (NF-κB) was first identified in 1986 as a transcription factor that binds to a 10 bp DNA element in kappa immunoglobulin light-chain enhancer in B cells [128]. The mammalian NF-κB family consists of 5 members: NF-κB1 (p50/p105), NF-κB2 (p52/p100), c-Rel, RelA (p65) and RelB (Fig. 1). RelA, c-Rel and RelB are synthesized in their mature forms and contain a transactivation domain that interacts with the transcriptional apparatus. On the other hand, NF-κB1 (p50/p105) and NF-κB2 (p52/p100) are synthesized in precursor forms (p100 and p105) which contain C-terminal ankyrin repeats that are proteolysed by the proteasome resulting in the production of mature proteins (p50 and p52). Both p50 and p52 contain a DNA binding domain but lack a transactivation domain. NF-κB proteins exist in unstimulated cells as homo-or heterodimers bound to IκB proteins. Whereas RelB forms only heterodimers, all the other proteins can form both homo-and heterodimers. NF-κB proteins are characterized by the presence of a highly conserved 300 amino acid Rel homology domain that is located toward the N terminus of the protein, and which is responsible for DNA binding, dimerization, and interaction with specific inhibitory factors known as IκB proteins [7,36].

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