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Cucurbitacin B Suppresses The Transactivation Activity of RelA/p65
Author(s) -
Jin Hongri,
Jin Xuejun,
Dat Nguyen Tien,
Lee Jung Joon
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.883.1
Subject(s) - transactivation , iκbα , xiap , nf κb , p50 , nfkb1 , phosphorylation , chemistry , cancer research , iκb kinase , apoptosis , microbiology and biotechnology , biology , gene expression , transcription factor , programmed cell death , gene , biochemistry , caspase
Cucurbitacin B, a natural triterpenoid is well known for its strong anticancer activity, and recent studies showed that cucurbitacicn B 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, cucurbitacin B 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 cucurbitacin B 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.