Phytochemicals targeting NF-κB signaling: Potential anti-cancer interventions

Nuclear factor kappa B (NF-kappa B) is a ubiquitous regulator of the signalome and is indispensable for various biological cell functions. NF-kappa B consists of five transcription factors that execute both cytoplasmic and nuclear signaling processes in cells. NF-kappa B is the only signaling molecule that governs both pro- and antiapoptotic, and pro- and anti-inflammatory responses. This is due to the canonical and non-canonical components of the NF-kappa B signaling pathway. Together, these pathways orchestrate cancer-related inflammation, hyperplasia, neoplasia, and metastasis. Non-canonical NF-kappa B pathways are particularly involved in the chemoresistance of cancer cells. In view of its pivotal role in cancer progression, NF-kappa B represents a potentially significant therapeutic target for modifying tumor cell behavior. Several phytochemicals are known to modulate NF-kappa B pathways through the stabilization of its inhibitor, I kappa B, by inhibiting phosphorylation and ubiquitination thereof. Several natural pharmacophores are known to inhibit the nuclear translocation of NF-kappa B and associated pro-inflammatory responses and cell survival pathways. In view of this and the high degree of specificity exhibited by various phytochemicals for the NF-kappa B component, we herein present an in-depth overview of these phytochemicals and discuss their mode of interaction with the NF-kappa B signaling pathways for controlling the fate of tumor cells for cancer-directed interventions. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of Xi'an Jiaotong University.