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

Authors
Type
Published Article
Journal
Biochemical Pharmacology
0006-2952
Publisher
Elsevier
Volume
78
Issue
6
Pages
592–606
Identifiers
DOI: 10.1016/j.bcp.2009.05.009
Source
LBMCC
Keywords
  • Biochemistry
  • Pharmacology

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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