The inhibition of TNF-α-induced NF-κB activation by marine natural products
The inhibition of TNF-α-induced NF-κB activation by marine natural products
复制标题
DOI：
10.1016/j.bcp.2009.05.009
复制
发表时间：
2009-09-15
影响因子：
5.8
通讯作者：
Diederich, Marc
中科院分区：
文献类型：
--
作者：
Folmer, Florence;Jaspars, Marcel;Diederich, Marc
NF-κ B的失调激活与癌症发展和炎性疾病相关。为了寻找新的NF-κ B抑制剂，我们从斐济海绵Rhabdastrella globostellata，海百合科Comanthus parvicirrus，软珊瑚Sarcophyton sp. nov.和Sinularia sp.的提取物中纯化和表征了化合物，结果表明，所选的纯化化合物对人白血病细胞系K562具有细胞毒性作用，抑制TNF-α诱导的NF-κ B-DNA结合以及TNF-α诱导的I κ B α降解和p50/p65的核转位。此外，我们观察到IKK β过表达诱导的NF-κ B活化的抑制。有趣的是，天然产物抑制IKK β激酶以及26 S蛋白酶体蛋白水解活性。(C)2009爱思唯尔公司All rights reserved.
The deregulated activation of NF-kappa B is associated with cancer development and inflammatory diseases. With an aim to find new NF-kappa B inhibitors, we purified and characterized compounds from extracts of the Fijian sponge Rhabdastrella globostellata, the crinoid Comanthus parvicirrus, the soft corals Sarcophyton sp. nov. and Sinularia sp., and the gorgonian Subergorgia sp. after an initial screening of 266 extracts from different marine origins.Results obtained show that selected purified compounds had a cytotoxic effect on the human leukaemia cell line K562, inhibited both TNF-alpha-induced NF-kappa B-DNA binding as well as TNF-alpha-induced I kappa B alpha degradation and nuclear translocation of p50/p65. Furthermore, we observed the inhibition of NF-kappa B activation induced by an overexpression of IKK beta. Interestingly, natural products inhibited IKK beta kinase as well as the 26S proteasome proteolytic activity. (C) 2009 Elsevier Inc. All rights reserved.