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      The inhibition of TNF-α-induced NF-κB activation by marine natural products

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          Abstract

          The deregulated activation of NF-kappaB is associated with cancer development and inflammatory diseases. With an aim to find new NF-kappaB 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-kappaB-DNA binding as well as TNF-alpha-induced IkappaBalpha degradation and nuclear translocation of p50/p65. Furthermore, we observed the inhibition of NF-kappaB activation induced by an overexpression of IKKbeta. Interestingly, natural products inhibited IKKbeta kinase as well as the 26S proteasome proteolytic activity.

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          Author and article information

          Journal
          Biochemical Pharmacology
          Biochemical Pharmacology
          Elsevier BV
          00062952
          September 2009
          September 2009
          : 78
          : 6
          : 592-606
          Article
          10.1016/j.bcp.2009.05.009
          19445900
          4f2eb044-e6f2-4e34-9fc2-ffbd1d515a5f
          © 2009

          https://www.elsevier.com/tdm/userlicense/1.0/

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