Functional Antagonism between NF-κB and Nuclear Receptors: Implications in Carcinogenesis and Strategies for Optimal Cancer Chemopreventive Interventions

Hyper-activation of nuclear factor kappa B (NF-κB) is germane to carcinogenesis by its fundamental implication in cellular de-differentiation and proliferation, the subversion of apoptosis, the promotion of neoangiogenesis, invasive growth and metastases. Conversely, the expression of multiple nuclear receptors (NRs), arbiters of cellular differentiation, decreases with progressive carcinogenesis. This review is a conceptual discussion of evidence to support NF-κB as the nexus between carcinogenesis and decreased NR expression. Furthermore, it synthesizes the thesis and antithesis of NR function in carcinogenesis and expounds on the functional antagonism between NRs and NF-κB as a basis for the chemopreventive activity of NR ligands. Finally, strategies for optimal chemopreventive interventions with NR ligands are discussed.