Styryl-lactone goniothalamin inhibits TNF-α-induced NF-κB activation

(R)-(+)-Goniothalamin (GTN), a styryl-lactone isolated from the medicinal plant Goniothalamus macrophyllus, exhibits pharmacological activities including cytotoxic and anti-inflammatory effects. In this study, GTN modulated TNF-alpha induced NF-kappa B activation. GTN concentrations up to 20 mu M showed low cytotoxic effects in K562 chronic myelogenous leukemia and in Jurkat T cells. Importantly, at these concentrations, no cytotoxicity was observed in healthy peripheral blood mononuclear cells. Our results confirmed that GTN inhibited tumor necrosis factor-alpha (TNF-alpha)-induced NF-kappa B activation in Jurkat and K562 leukemia cells at concentrations as low as 5 mu M as shown by reporter gene assays and western blots. Moreover, GTN down-regulated translocation of the p50/p65 heterodimer to the nucleus, prevented binding of NF-kappa B to its DNA response element and reduced TNF-alpha-activated interleukin-8 (IL-8) expression. In conclusion, GTN inhibits TNF-alpha-induced NF-kappa B activation at non-apoptogenic concentrations in different leukemia cell models without presenting toxicity towards healthy blood cells underlining the anti-leukemic potential of this natural compound. (C) 2013 Elsevier Ltd. All rights reserved.