title: Inhibition of the NF-κB signaling pathway by a novel heterocyclic curcumin analogue.
abstract: In this study a series of curcumin analogues were evaluated for their ability to inhibit the activation of NF-κΒ, a transcription factor at the crossroads of cancer-inflammation. Our novel curcumin analogue BAT3 was identified to be the most potent NF-κB inhibitor and EMSA assays clearly showed inhibition of NF-κB/DNA-binding in the presence of BAT3, in agreement with reporter gene results. Immunofluorescence experiments demonstrated that BAT3 did not seem to prevent nuclear p65 translocation, so our novel analogue may interfere with NF-κB/DNA-binding or transactivation, independently of IKK2 regulation and NF-κB-translocation. Gene expression studies on endogenous NF-κB target genes revealed that BAT3 significantly inhibited TNF-dependent transcription of IL6, MCP1 and A20 genes, whereas an NF-κB independent target gene heme oxygenase-1 remained unaffected. In conclusion, we demonstrate that BAT3 seems to inhibit different cancer-related inflammatory targets in the NF-κB signaling pathway through a different mechanism in comparison to similar analogues, previously reported.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece. akatsori@pharm.auth.gr.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Katsori
authors.affiliation: Laboratory of Protein Chemistry, Proteomics and Epigenetic Signaling (PPES), Department of Biomedical Sciences, University of Antwerp, Wilrijk 2610, Belgium. ajay.palagani@ua.ac.be.
authors.forename: Ajay
authors.initials: A
authors.lastname: Palagani
authors.affiliation: Laboratory of Eukaryotic Gene Expression and Signal Transduction (LEGEST), Department of Physiology, University of Ghent, Ghent 9000, Belgium. nadia.bougarne@vib-ugent.be.
authors.forename: Nadia
authors.initials: N
authors.lastname: Bougarne
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece. hadjipav@pharm.auth.gr.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Hadjipavlou-Litina
authors.affiliation: Laboratory of Eukaryotic Gene Expression and Signal Transduction (LEGEST), Department of Physiology, University of Ghent, Ghent 9000, Belgium. Guy.Haegeman@UGent.be.
authors.forename: Guy
authors.initials: G
authors.lastname: Haegeman
authors.affiliation: Laboratory of Protein Chemistry, Proteomics and Epigenetic Signaling (PPES), Department of Biomedical Sciences, University of Antwerp, Wilrijk 2610, Belgium. wim.vandenberghe@ua.ac.be.
authors.forename: Wim
authors.initials: W
authors.lastname: Vanden Berghe
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002460:Cell Line; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D006571:Heterocyclic Compounds; D016328:NF-kappa B; D004247:DNA; D003474:Curcumin