The aromatic ketone 4 '-hydroxychalcone inhibits TNF alpha-induced NF-kappa B activation via proteasome inhibition

作者：Orlikova Barbora; Tasdemir Deniz; Golais Frantisek; Dicato Mario; Diederich Marc^*

来源：Biochemical Pharmacology, 2011, 82(6): 620-631.

DOI：10.1016/j.bcp.2011.06.012

• Polyphenol
• Chalcone
• NF-kappa B
• Inflammation
• Cancer

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 TNF alpha-induced NF-kappa B 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 TNF alpha-dependent degradation of I kappa B alpha and subsequently prevents p50/p65 nuclear translocation leading to 4'-hydroxychalcone-inhibited expression of NF-kappa B target genes. Most importantly, inhibition of NF-kappa B 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.

• 出版日期2011-9-15