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Title 

Cucurbitacin B suppresses the transactivation activity of RelA/p65

Authors 

H R JinX JinN T DatJung Joon Lee

Publisher 

Wiley-Blackwell

Issue Date 

2011

Citation 

Journal of Cellular Biochemistry, vol. 112, no. 6, pp. 1643-1650

Keywords 

AKTanti-apoptosiscucurbitacin BNF-κBRELA/p65transactivation

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.

ISSN 

0730-2312

Link 

http://dx.doi.org/10.1002/jcb.23078

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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