Cucurbitacin B Suppresses the Transactivation Activity of RelA/p65
Cucurbitacin B Suppresses the Transactivation Activity of RelA/p65
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DOI：
10.1002/jcb.23078
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发表时间：
2011-06-01
影响因子：
4
通讯作者：
Lee, Jung Joon
中科院分区：
文献类型：
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作者：
Jin, Hong Ri;Jin, Xuejun;Lee, Jung Joon
葫芦素B是一种天然的三萜类化合物，具有很强的抗癌活性，最近的研究表明该化合物能抑制JAK/STAT3途径。在这项研究中，我们首次证明了葫芦素B也是一种有效的核因子-kappa B激活的抑制剂。我们的结果表明，葫芦素B以剂量依赖的方式抑制肿瘤坏死因子-α诱导的报告基因和核转录因子-kappaB的表达，但不能阻止刺激诱导的IkBα的降解或核转位和核转录因子-kappa B的DNA结合活性。另一方面，葫芦素B不仅剂量依赖地抑制由relA/p65过表达诱导的核转录因子-kappaB的激活，而且抑制由relA/p65亚基诱导的核转录活性。这是激活活动所必需的。因此，葫芦素B抑制肿瘤坏死因子-α诱导的c-IAP1、c-IAP2、XIAP、TRAF1和TRAF2等依赖于核因子-kappa B的抗凋亡蛋白的表达，并敏化肿瘤坏死因子-α诱导的细胞死亡。综上所述，我们的结果表明，葫芦素B可以作为一种有价值的候选分子来干预依赖于核因子-kappaB的病理条件，如癌症。J.细胞。生物化学。112：1643-1650,2011。(C)2011年Wiley-Liss，Inc.
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-kappa B activation. Our results showed that cucurbitacin B inhibited TNF-alpha-induced expression of NF-kappa B reporter gene and NF-kappa B target genes in a dose-dependent manner, however, it did not prevent either stimuli-induced degradation of IkB alpha or nuclear translocation and DNA-binding activity of NF-kappa B. On the other hand, cucurbitacin B dose-dependently suppressed not only NF-kappa B activation induced by overexpression of RelA/p65 but also transactivation activity of RelA/p65 subunit of NF-kappa B. Consistently, treatment of HeLa cells with the compound significantly suppressed TNF-alpha-induced activation of Akt and phosphorylation of Ser536 in RelA/p65, which is required for transactivation activity. Consequently, cucurbitacin B inhibited TNF-alpha-induced expression of NF-kappa B-dependent anti-apoptotic proteins such as c-IAP1, c-IAP2, XIAP, TRAF1, and TRAF2 and sensitized TNF-alpha-induced cell death. Taken together, our results demonstrated that cucurbitacin B could be served as a valuable candidate for the intervention of NF-kappa B-dependent pathological condition such as cancer. J. Cell. Biochem. 112: 1643-1650, 2011. (C) 2011 Wiley-Liss, Inc.