TY - JOUR
T1 - The inhibition of TNF-α-induced NF-κB activation by marine natural products
AU - Folmer, Florence
AU - Jaspars, Marcel
AU - Solano, Godofredo
AU - Cristofanon, Silvia
AU - Henry, Estelle
AU - Tabudravu, Jioji
AU - Black, Kenny
AU - Green, David H.
AU - Küpper, Frithjof C.
AU - Aalbersberg, William
AU - Feussner, Klaus
AU - Dicato, Mario
AU - Diederich, Marc
PY - 2009/9/15
Y1 - 2009/9/15
N2 - The deregulated activation of NF-κB is associated with cancer development and inflammatory diseases. With an aim to find new NF-κB 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-α-induced NF-κB-DNA binding as well as TNF-α-induced IκBα degradation and nuclear translocation of p50/p65. Furthermore, we observed the inhibition of NF-κB activation induced by an overexpression of IKKβ. Interestingly, natural products inhibited IKKβ kinase as well as the 26S proteasome proteolytic activity.
AB - The deregulated activation of NF-κB is associated with cancer development and inflammatory diseases. With an aim to find new NF-κB 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-α-induced NF-κB-DNA binding as well as TNF-α-induced IκBα degradation and nuclear translocation of p50/p65. Furthermore, we observed the inhibition of NF-κB activation induced by an overexpression of IKKβ. Interestingly, natural products inhibited IKKβ kinase as well as the 26S proteasome proteolytic activity.
KW - Anti-cancer drug discovery
KW - Marine natural product
KW - NF-κB
UR - http://www.scopus.com/inward/record.url?scp=67749109784&partnerID=8YFLogxK
U2 - 10.1016/j.bcp.2009.05.009
DO - 10.1016/j.bcp.2009.05.009
M3 - Article
C2 - 19445900
AN - SCOPUS:67749109784
SN - 0006-2952
VL - 78
SP - 592
EP - 606
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 6
ER -