Pro-apoptotic role of NF-κB: Implications for cancer therapy

Nuclear factor-κB (NF-κB) is generally viewed as anti-apoptotic and oncogenic, leading to a quest for its inhibitors. However, recent evidence suggests that in some situations NF-κB may promote apoptosis. Depending on the specific cell type and the stimulus involved, NF-κB activation may lead to either anti- or pro-apoptotic response. Both these effects can be mediated by NF-κB in a context-dependent manner by selectively regulating its target genes. In this review, we discuss the evidence for NF-κB's pro-apoptotic role and explore the possible mechanisms behind it. We emphasize that rather than trying to inhibit NF-κB in cancer therapy, agents should be developed to unleash its pro-apoptotic ability.