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

• Published in: Food and Chemical Toxicology
• Main Author: Orlikova B.; Schumacher M.; Juncker T.; Yan C.C.; Inayat-Hussain S.H.; Hajjouli S.; Cerella C.; Dicato M.; Diederich M.
• Format: Article
• Language: English
• Published: 2013
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84881002603&doi=10.1016%2fj.fct.2013.06.051&partnerID=40&md5=408f7fdb3f6bb47a312fdc6bc5858ec2

(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-α induced NF-κB activation. GTN concentrations up to 20. μM 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-α (TNF-α)-induced NF-κB activation in Jurkat and K562 leukemia cells at concentrations as low as 5. μM 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-κB to its DNA response element and reduced TNF-α-activated interleukin-8 (IL-8) expression. In conclusion, GTN inhibits TNF-α-induced NF-κB 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. © 2013 Elsevier Ltd.