1. Styryl-lactone goniothalamin inhibits TNF-α-induced NF-κB activation.
- Author
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Orlikova B, Schumacher M, Juncker T, Yan CC, Inayat-Hussain SH, Hajjouli S, Cerella C, Dicato M, and Diederich M
- Subjects
- Anti-Inflammatory Agents, Non-Steroidal adverse effects, Anti-Inflammatory Agents, Non-Steroidal isolation & purification, Antineoplastic Agents, Phytogenic adverse effects, Antineoplastic Agents, Phytogenic isolation & purification, Cell Nucleus drug effects, Cell Nucleus metabolism, Cells, Cultured, Genes, Reporter drug effects, Goniothalamus chemistry, Humans, Interleukin-8 antagonists & inhibitors, Interleukin-8 metabolism, Jurkat Cells, K562 Cells, Leukocytes, Mononuclear cytology, Leukocytes, Mononuclear drug effects, Malaysia, NF-kappa B agonists, NF-kappa B antagonists & inhibitors, Neoplasm Proteins antagonists & inhibitors, Neoplasm Proteins genetics, Neoplasm Proteins metabolism, Plant Roots chemistry, Protein Transport drug effects, Pyrones adverse effects, Pyrones isolation & purification, Recombinant Proteins chemistry, Recombinant Proteins metabolism, Response Elements drug effects, Tumor Necrosis Factor-alpha genetics, Tumor Necrosis Factor-alpha metabolism, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Antineoplastic Agents, Phytogenic pharmacology, Drug Discovery, Leukemia drug therapy, NF-kappa B metabolism, Pyrones pharmacology, Tumor Necrosis Factor-alpha antagonists & inhibitors
- 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., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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