Natural Dietary Compounds Targeting NF-κB Signaling in Cancer: Implications for Nutrition-Based Prevention and Therapy

Dysregulation of the nuclear factor kappa B (NF-κB) signaling pathway is closely associated with inflammation-driven carcinogenesis, tumor progression and resistance to conventional therapies. Sustained NF-κB activation enhances malignant cell survival, proliferation and immune evasion by promoting proinflammatory and antiapoptotic gene expression. This review aims to critically evaluate natural dietary compounds that modulate NF-κB signaling and explore their translational relevance in cancer prevention and therapy. We analyzed key classes of phytochemicals such as polyphenols (curcumin, resveratrol), flavonoids (EGCG, quercetin), alkaloids (berberine), and terpenoids (celastrol), focusing on their molecular mechanisms of NF-κB inhibition, preclinical anticancer efficacy, and emerging strategies to overcome pharmacokinetic limitations. Preclinical evidence consistently demonstrates that these compounds inhibit NF-κB activity by targeting upstream kinases, preventing nuclear translocation, and suppressing downstream protumorigenic gene expression. Notably, advances in nanotechnology-based delivery systems, including liposomes and polymeric nanoparticles, have markedly enhanced the stability, bioavailability, and tumor-specific delivery of these agents in vivo. In conclusion, natural NF-κB-targeting compounds offer a promising multitargeted strategy for integrative cancer therapy. Continued development of optimized formulations and well-designed clinical trials will be essential to translate their potential into effective nutraceutical or adjuvant interventions in oncology.