Nuclear factor-kappa B and cancer: its role in prevention and therapy

Cancer is a hyperproliferative disorder in which invasion and angiogenesis lead to tumor metastasis. Several genes that mediate tumorigenesis and metastasis are regulated by a nuclear transcription factor, nuclear factor kappa B (NF-κB). A heterotrimeric complex consisting of p50, p65, and IκBα, NF-κB is present in its inactive state in the cytoplasm. When NF-κB is activated, IκBα is degraded and p50–p65 heterodimer is translocated to the nucleus, binds the DNA (at the promoter region), and activates gene. Research within the last few years has revealed that NF-κB is activated by carcinogens, tumor promoters, inflammatory cytokines, and by chemotherapeutic agents. The activation of NF-κB can suppress apoptosis, thus promoting chemoresistance and tumorigenesis. Interestingly, however, most chemopreventive agents appear to suppress the activation of the NF-κB through inhibition of NF-κB signaling pathway. These chemopreventive agents also sensitize the tumors to chemotherapeutic agents through abrogation of NF-κB activation. Overall, these observations suggest that NF-κB is an ideal target for chemoprevention and chemosensitization. This article reviews evidence supporting this hypothesis. [Copyright &y& Elsevier]