Brusatol-induced HL-60 cell differentiation involves NF-κB activation

Muriel Cuendet, Joell J. Gills, John M. Pezzuto

Research output: Contribution to journalArticle

Abstract

Brusatol, a quassinoid isolated from the fruit of Brucea javanica, induces cell differentiation with various leukemic cell lines in the concentration range of 5-25 ng/ml. To investigate its mechanism of action, cultured HL-60 cells were treated with brusatol (25 ng/ml) for various periods of time and qualitatively analyzed for differential gene expression using a cDNA macroarray. As suggested by these preliminary data, we investigated the effect of brusatol on the Rel/nuclear factor-kappa B (NF-κB) family members and their role in HL-60 cell differentiation. When cells were treated with brusatol (25 ng/ml), p100/p52, p105/p50 and p65 mRNA were found to be up-regulated with a maximum after 8 h. As determined by electrophoretic mobility shift assays (EMSA), NF-κB was activated, involving p50 and p65. Moreover, immunoblots showed a decrease of IκBα and generation of the phosphorylated form of IκBα in whole cell lysates. Cell differentiation induced by brusatol was inhibited by SN50, a NF-κB translocation inhibitor. These results strongly suggest that brusatol induces activation of NF-κB and the activation and translocation of NF-κB into the nucleus is responsible for promoting HL-60 cell differentiation.

Original languageEnglish (US)
Pages (from-to)43-50
Number of pages8
JournalCancer Letters
Volume206
Issue number1
DOIs
StatePublished - Mar 31 2004
Externally publishedYes

Keywords

  • Brusatol
  • Cell differentiation
  • NF-κB

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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