Bharangin, a diterpenoid quinonemethide, abolishes constitutive and inducible nuclear factor-κB (NF-κB) activation by modifying p65 on cysteine 38 residue and reducing inhibitor of nuclear factor-κB α kinase activation, leading to suppression of NF-κB-regulated gene expression and sensitization of tumor cells to chemotherapeutic agents.

ABSTRACT: Although inflammatory pathways have been linked with various chronic diseases including cancer, identification of an agent that can suppress these pathways has therapeutic potential. Herein we describe the identification of a novel compound bharangin, a diterpenoid quinonemethide that can suppress pro-inflammatory pathways specifically. We found that bharangin suppresses nuclear factor (NF)-κB activation induced by pro-inflammatory cytokine, tumor promoter, cigarette smoke, and endotoxin. Inhibition of NF-κB activation was mediated through the suppression of phosphorylation and degradation of inhibitor of nuclear factor-κB (IκBα); inhibition of IκBα kinase activation; and suppression of p65 nuclear translocation, and phosphorylation. The diterpenoid inhibited binding of p65 to DNA. A reduc

SUBMITTER: Gupta SC 

PROVIDER: S-EPMC3198918 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature