Article (Scientific journals)
Heteronemin, a spongean sesterterpene, inhibits TNF alpha-induced NF-kappa B activation through proteasome inhibition and induces apoptotic cell death
Schumacher, Marc; Cerella, Claudia; Eifes, Serge et al.
2010In Biochemical Pharmacology, 79 (4), p. 610-22
Peer reviewed
 

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Abstract :
[en] In this study, we investigated the biological effects of heteronemin, a marine sesterterpene isolated from the sponge Hyrtios sp. on chronic myelogenous leukemia cells. To gain further insight into the molecular mechanisms triggered by this compound, we initially performed DNA microarray profiling and determined which genes respond to heteronemin stimulation in TNFalpha-treated cells and which genes display an interaction effect between heteronemin and TNFalpha. Within the differentially regulated genes, we found that heteronemin was affecting cellular processes including cell cycle, apoptosis, mitogen-activated protein kinases (MAPKs) pathway and the nuclear factor kappaB (NF-kappaB) signaling cascade. We confirmed in silico experiments regarding NF-kappaB inhibition by reporter gene analysis, electrophoretic mobility shift analysis and I-kappaB degradation. In order to assess the underlying molecular mechanisms, we determined that heteronemin inhibits both trypsin and chymotrypsin-like proteasome activity at an IC(50) of 0.4 microM. Concomitant to the inhibition of the NF-kappaB pathway, we also observed a reduction in cellular viability. Heteronemin induces apoptosis as shown by annexin V-FITC/propidium iodide-staining, nuclear morphology analysis, pro-caspase-3, -8 and -9 and poly(ADP-ribose) polymerase (PARP) cleavage as well as truncation of Bid. Altogether, results show that this compound has potential as anti-inflammatory and anti-cancer agent.
Disciplines :
Life sciences: Multidisciplinary, general & others
Identifiers :
UNILU:UL-ARTICLE-2012-430
Author, co-author :
Schumacher, Marc
Cerella, Claudia
Eifes, Serge ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Chateauvieux, Sebastien
Morceau, Franck
Jaspars, Marcel
Dicato, Mario
Diederich, Marc
External co-authors :
yes
Language :
English
Title :
Heteronemin, a spongean sesterterpene, inhibits TNF alpha-induced NF-kappa B activation through proteasome inhibition and induces apoptotic cell death
Publication date :
2010
Journal title :
Biochemical Pharmacology
ISSN :
0006-2952
Publisher :
Elsevier Science, Oxford, United Kingdom
Volume :
79
Issue :
4
Pages :
610-22
Peer reviewed :
Peer reviewed
Available on ORBilu :
since 30 March 2016

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