title: Cucurbitacin B suppresses the transactivation activity of RelA/p65.
abstract: Cucurbitacin B, a natural triterpenoid is well-known for its strong anticancer activity, and recent studies showed that the compound inhibits JAK/STAT3 pathway. In this study, we demonstrate for the first time that cucurbitacin B is also a potent inhibitor of NF-κB activation. Our results showed that cucurbitacin B inhibited TNF-α-induced expression of NF-κB reporter gene and NF-κB target genes in a dose-dependent manner, however, it did not prevent either stimuli-induced degradation of IκBα or nuclear translocation and DNA-binding activity of NF-κB. On the other hand, cucurbitacin B dose-dependently suppressed not only NF-κB activation induced by overexpression of RelA/p65 but also transactivation activity of RelA/p65 subunit of NF-κB. Consistently, treatment of HeLa cells with the compound significantly suppressed TNF-α-induced activation of Akt and phosphorylation of Ser536 in RelA/p65, which is required for transactivation activity. Consequently, cucurbitacin B inhibited TNF-α-induced expression of NF-κB-dependent anti-apoptotic proteins such as c-IAP1, c-IAP2, XIAP, TRAF1, and TRAF2 and sensitized TNF-α-induced cell death. Taken together, our results demonstrated that cucurbitacin B could be served as a valuable candidate for the intervention of NF-κB-dependent pathological condition such as cancer.
authors.affiliation: Center for Molecular Cancer Research, Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungbuk 363-883, Republic of Korea.
authors.forename: Hong Ri
authors.initials: HR
authors.lastname: Jin
authors.forename: Xuejun
authors.initials: X
authors.lastname: Jin
authors.forename: Nguyen Tien
authors.initials: NT
authors.lastname: Dat
authors.forename: Jung Joon
authors.initials: JJ
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D006367:HeLa Cells; D006801:Humans; D016133:Polymerase Chain Reaction; D051996:Transcription Factor RelA / Q000378:metabolism*; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D051996:Transcription Factor RelA; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C041246:cucurbitacin B