title: Styryl-lactone goniothalamin inhibits TNF-α-induced NF-κB activation.
abstract: (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.
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Fondation de Recherche Cancer et Sang, Hôpital Kirchberg, Luxembourg, Luxembourg.
authors.forename: Barbora
authors.initials: B
authors.lastname: Orlikova
authors.forename: Marc
authors.initials: M
authors.lastname: Schumacher
authors.forename: Tom
authors.initials: T
authors.lastname: Juncker
authors.forename: Choo Chee
authors.initials: CC
authors.lastname: Yan
authors.forename: Salmaan H
authors.initials: SH
authors.lastname: Inayat-Hussain
authors.forename: Shéhérazade
authors.initials: S
authors.lastname: Hajjouli
authors.forename: Claudia
authors.initials: C
authors.lastname: Cerella
authors.forename: Mario
authors.initials: M
authors.lastname: Dicato
authors.forename: Marc
authors.initials: M
authors.lastname: Diederich
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D055808:Drug Discovery; D017930:Genes, Reporter / Q000187:drug effects; D054335:Goniothalamus / Q000737:chemistry; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019169:Jurkat Cells; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008296:Malaysia; D016328:NF-kappa B / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018517:Plant Roots / Q000737:chemistry; D021381:Protein Transport / Q000187:drug effects; D011753:Pyrones / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D020218:Response Elements / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000972:Antineoplastic Agents, Phytogenic; C508606:CXCL8 protein, human; D016209:Interleukin-8; D016328:NF-kappa B; D009363:Neoplasm Proteins; D011753:Pyrones; D011994:Recombinant Proteins; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C103280:goniothalamin
keywords: Anti-cancer drug discovery; BSA; Cancer; EMSA; GTN; IKKβ; IL-8; Inflammation; NF-κB; NF-κB inducing kinase; NIK; PBMC; Plant natural product; TAB1; TAK1; TAK1-binding protein 1; TNF-α; TNF-α-receptor-1; TNFR-1; TNFR-1 associated death domain; TNFR-associated factor-2; TRADD; TRAF2; bovine serum albumin; electrophoretic mobility shift assay; goniothalamin; inhibitor of κB kinase beta; interleukine-8; nuclear factor κB; peripheral blood mononuclear cells; tumor growth factor activated kinase 1; tumor necrosis factor alpha