The inhibition of TNF-a induced NF-kB activation by marine natural products

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.