title: The aromatic ketone 4'-hydroxychalcone inhibits TNFα-induced NF-κB activation via proteasome inhibition.
abstract: Chalcones are aromatic ketones, known to exhibit anti-microbial, anti-inflammatory and anti-cancer activities. The aim of this study was to investigate the anti-inflammatory and anti-cancer activity of 4'-hydroxychalcone. Here, we report that 4'-hydroxychalcone inhibits TNFα-induced NF-κB pathway activation in a dose-dependent manner. To investigate the underlying molecular mechanisms we demonstrate that 4'-hydroxychalcone inhibits proteasome activity in a dose-dependent manner but has no effect on IKK activity. Results show that 4'-hydroxychalcone inhibits TNFα-dependent degradation of IκBα and subsequently prevents p50/p65 nuclear translocation leading to 4'-hydroxychalcone-inhibited expression of NF-κB target genes. Most importantly, inhibition of NF-κB activation by 4'-hydroxychalcone is not leukemia cell-type specific and has no significant effect on non-transformed cell viability, thus highlighting the compound's potential in both prevention and treatment.
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Fondation de Recherche Cancer et Sang, Hôpital Kirchberg, 9 Rue Edward Steichen, 2540 Luxembourg, Luxembourg.
authors.forename: Barbora
authors.initials: B
authors.lastname: Orlikova
authors.forename: Deniz
authors.initials: D
authors.lastname: Tasdemir
authors.forename: Frantisek
authors.initials: F
authors.lastname: Golais
authors.forename: Mario
authors.initials: M
authors.lastname: Dicato
authors.forename: Marc
authors.initials: M
authors.lastname: Diederich
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001692:Biological Transport; D015153:Blotting, Western; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008156:Luciferases / Q000235:genetics; D015394:Molecular Structure; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D061988:Proteasome Inhibitors; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D047188:Chalcones; D016328:NF-kappa B; D061988:Proteasome Inhibitors; D014409:Tumor Necrosis Factor-alpha; C561448:4'-hydroxychalcone; D008156:Luciferases; D051550:I-kappa B Kinase