cardamonin and Leukemia

Cardamonin, the chalcone class, is one of the natural components from the spicy herbaceous plant (

Topics: Animals; Apoptosis; Cell Cycle Checkpoints; Cell Line, Tumor; Chalcones; Endoplasmic Reticulum Chaperone BiP; Gene Expression Regulation, Developmental; Leukemia; Mice

A toll-like receptor 4 (TLR-4) ligand, lipopolysaccharide (LPS) not only activates expression and secretion of inflammatory cytokines, but it also often shows toxicity in monocytes. Whether an oncogenic protein, β-catenin, is positively involved in LPS-induced cytotoxicity in a mouse leukemic monocyte cell line, RAW 264.7, was examined. TWS119, a GSK-3β inhibitor, increased LPS-induced β-catenin accumulation in the nucleus and augmented LPS-induced cytotoxicity. Cardamonin, a β-catenin inhibitor, inhibited LPS-induced β-catenin accumulation in the nucleus and reduced LPS-induced cytotoxicity. To confirm that β-catenin is involved in LPS-induced cytotoxicity, silencing of β-catenin expression by siRNA was carried out. The results were that knockdown of β-catenin reduced LPS-induced cytotoxicity. Interestingly, Cardamonin treatment or β-catenin silencing reduced LPS-induced endoplasmic reticulum (ER) stress responses such as PERK and e1F-2α phosphorylation and CHOP expression. Moreover, TWS119 increased LPS-induced ER stress responses. On the basis of these results, the oncogenic protein β-catenin is considered to be positively involved in LPS-induced cytotoxicity, possibly by downregulating ER stress responses.

Topics: Animals; beta Catenin; Cell Line; Cell Line, Tumor; Chalcones; Drug Interactions; Endoplasmic Reticulum Stress; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Leukemia; Lipopolysaccharides; Mice; Monocytes; Phosphorylation; Pyrimidines; Pyrroles; RNA, Small Interfering; Toll-Like Receptor 4; Transfection