The aromatic ketone 4′-hydroxychalcone inhibits TNFα-induced NF-κBactivation proteasome inhibition

Barbora Orlikova (1) , Deniz Tasdemir (2) , Frantisek Golais (3) , Mario Dicato (1) , Marc Diederich (1)

1 Fondation de Recherche Cancer et Sang - Hôpital Kirchberg
2 UCL - University College of London [London]
3 Department of Microbiology and Virology

Chalconesare aromatic ketones,known toexhibit 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 leukemiacell-type specific and has no significant effect on non-transformed cell viability, thus highlighting the compound's potential in both prevention and treatment.

Mots clés: Polyphenol; chalcone; NF-κB; inflammation; cancer

Domaines: Pharmacologie

Barbora Orlikova, Deniz Tasdemir, Frantisek Golais, Mario Dicato, Marc Diederich. The aromatic ketone 4′-hydroxychalcone inhibits TNFα-induced NF-κBactivation proteasome inhibition. Biochemical Pharmacology, 2011, 82 (6), pp.620. ⟨10.1016/j.bcp.2011.06.012⟩. ⟨hal-00722843⟩