Inhibitory mechanism of pure curcumin on Wilms' tumor 1 (WT1) gene expression through the PKCα signaling pathway in leukemic K562 cells

The aim of this study was to investigate the inhibitory mechanism of pure curcumin on WT1 expression in leukemic K562 cells. Pure curcumin suppressed WT1 expression, independent of effects on protein degradation or WT1 mRNA stability. Chromatin immunoprecipitation and reporter gene assays indicate that pure curcumin treatment attenuates WT1 auto-regulation. Interestingly, PKCa inhibition mimicks the repressive effects of pure curcumin in K562 cells. Conversely, myristoylated PKC alpha over-expression increased WT1 expression and reversed the inhibitory effect of pure curcumin. Our study indicates that pure curcumin attenuates WT1 auto-regulatory function through inhibition of PKC alpha signaling in K562 cells. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.