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

FEBS Lett. 2011 Jul 21;585(14):2235-42. doi: 10.1016/j.febslet.2011.05.043. Epub 2011 Jun 7.

Abstract

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, PKCα inhibition mimicks the repressive effects of pure curcumin in K562 cells. Conversely, myristoylated PKCα 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 PKCα signaling in K562 cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Curcumin / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Genes, Reporter
  • Humans
  • K562 Cells* / drug effects
  • K562 Cells* / physiology
  • Promoter Regions, Genetic
  • Protein Kinase C-alpha / metabolism*
  • Signal Transduction / drug effects*
  • WT1 Proteins / genetics*
  • WT1 Proteins / metabolism

Substances

  • Antineoplastic Agents
  • WT1 Proteins
  • Protein Kinase C-alpha
  • Curcumin