The Effects of Nimbolide on NF-κB Signaling
NF-κB comprises a family of transcription factors involved in the regulation of a wide variety of biological responses. NF-κB has a well-known function in the regulation of immune responses and inflammation, but growing evidence supports a major role in oncogenesis. NF-κB regulates the expression of genes involved in many processes that play a key role in the development and progression of cancer, such as proliferation, migration, and apoptosis [44, 45]. This transcription factor is localized in the cytosol and is blocked by Iκb. Activation of NF-κB may result from different signaling pathways triggered by a variety of cytokines, growth factors, and tyrosine kinases [44].
Recently, it was studied that nimbolide exerts potent anticancer effects in HepG2 cells by inhibiting NF-κB activation and its downstream events, such as activation of the Wnt/β-catenin pathway and apoptosis evasion. Inhibitors of NF-κB which can block several signalling pathway, have developed as a successful candidates for novel anti-cancer regimens. Thus, nimbolide, by targeting multiple components of the NF-κB signaling pathway to inhibit tumor progression, is a promising agent for cancer prevention and therapy [17]. Gupta et al. [16] found that suppression of NF-κB activation by nimbolide was caused by inhibition of IKK, which led to suppression of IκB phosphorylation and degradation, nuclear translocation, DNA binding, and gene transcription in myeloid and leukemic cells. Nimbolide significantly decreased the protein expression of IKKα, IKKβ, and NF-κB in breast cancer cell lines [46].