title: The inhibition of TNF-alpha-induced NF-kappaB activation by marine natural products.
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.
authors.affiliation: Department of Chemistry, University of Aberdeen, Old Aberdeen, UK.
authors.forename: Florence
authors.initials: F
authors.lastname: Folmer
authors.forename: Marcel
authors.initials: M
authors.lastname: Jaspars
authors.forename: Godofredo
authors.initials: G
authors.lastname: Solano
authors.forename: Silvia
authors.initials: S
authors.lastname: Cristofanon
authors.forename: Estelle
authors.initials: E
authors.lastname: Henry
authors.forename: Jioji
authors.initials: J
authors.lastname: Tabudravu
authors.forename: Kenny
authors.initials: K
authors.lastname: Black
authors.forename: David H
authors.initials: DH
authors.lastname: Green
authors.forename: Frithjof C
authors.initials: FC
authors.lastname: Küpper
authors.forename: William
authors.initials: W
authors.lastname: Aalbersberg
authors.forename: Klaus
authors.initials: K
authors.lastname: Feussner
authors.forename: Mario
authors.initials: M
authors.lastname: Dicato
authors.forename: Marc
authors.initials: M
authors.lastname: Diederich
mesh_terms: D001688:Biological Products / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D020672:I-kappa B Proteins / Q000737:chemistry; D008386:Marine Biology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D001688:Biological Products; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha