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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 TNFα-treated cells and which genes display an interaction effect between heteronemin and TNFα. 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 κB (NF-κB) signaling cascade. We confirmed in silico experiments regarding NF-κB inhibition by reporter gene analysis, electrophoretic mobility shift analysis and I-κB degradation. In order to assess the underlying molecular mechanisms, we …