Enhancement of 1α, 25-dihydroxyvitamin D3-induced differentiation of human leukaemia HL-60 cells into monocytes by parthenolide via inhibition of NF-κB activity

S. N. Kang, S. H. Kim, S. W. Chung, M. H. Lee, H. J. Kim, T. S. Kim

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

1. Transcription factors such as NF-κB provide powerful targets for drugs to use in the treatment of cancer. In this report parthenolide (PT), a sesquiterpene lactone of herbal remedies such as feverfew (Tanacetum parthenium) with NF-κB inhibitory activity, markedly increased the degree of human leukaemia HL-60 cell differentiation when simultaneously combined with 5 nM 1α, 25-dihydroxyvitamin D3 (1, 25-(OH)2D3). PT by itself did not induce HL-60 cell differentiation. 2. Cytofluorometric analysis indicated that PT stimulated 1, 25-(OH)2D3-induced differentiation of HL-60 cells predominantly into monocytes. 3. Pretreatment of HL-60 cells with PT before the 1, 25-(OH)2D3 addition also potentiated the 1, 25-(OH)2D3-induced HL-60 cell differentiation in both a dose- and a time-dependent manner, in which the enhanced levels of cell differentiation closely correlated with the inhibitory levels of NF-κB binding activity by PT. 4. In contrast, santonin, a sesquiterpene lactone without an inhibitory activity of NF-κB binding to the κB sites, did not enhance the 1, 25-(OH)2D3-induced HL-60 cell differentiation. 5. In transfection experiments, PT enhanced 1, 25-(OH)2D3-induced VDRE-dependent promoter activity. Furthermore, PT restored 1, 25-(OH)2D3-induced VDRE-dependent promoter activity inhibited by TNF-α, an activator of NF-κB signalling pathway. 6. These results indicate that PT strongly potentiates the 1, 25-(OH)2D3-induced HL-60 cell differentiation into monocytes via the inhibition of NF-κB activity and provide evidence that inhibition of NF-κB activation can be a pre-requisite to the efficient entry of promyelocytic leukaemia cells into a differentiation pathway.

Original languageEnglish
Pages (from-to)1235-1244
Number of pages10
JournalBritish Journal of Pharmacology
Volume135
Issue number5
DOIs
Publication statusPublished - 2002 Jan 1

Keywords

  • Differentiation
  • Nuclear factor-κB
  • Parthenolide
  • Sesquiterpene lactone

ASJC Scopus subject areas

  • Pharmacology

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