Potentiation of 1,25-dihydroxyvitamin D3-induced differentiation of human promyelocytic leukemia cells into monocytes by costunolide, a germacranolide sesquiterpene lactone

Seung H. Kim, So N. Kang, Hyeoung J. Kim, Tae S. Kim

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39 Citations (Scopus)

Abstract

Costunolide, a germacranolide sesquiterpene lactone that exists in several medicinal plants, is known to be a possible anti-cancer and chemopreventive agent for tumorigenesis. In this report, we investigated the effect of costunolide on cellular differentiation in the human promyelocytic leukemia HL-60 cell culture system. Costunolide markedly increased the degree of HL-60 leukemia cell differentiation when simultaneously combined with 5 nM 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). Costunolide by itself had very weak effects on the differentiation of HL-60 cells. Cytofluorometric analysis and cell morphologic studies indicated that costunolide potentiated 1,25-(OH)2D3-induced cell differentiation predominantly into monocytes. Inhibitors for PKC, PI3-K, and ERK markedly inhibited HL-60 cell differentiation induced by costunolide in combination with 1,25-(OH)2D3. In addition, pretreatment of HL-60 cells with costunolide before the 1,25-(OH)2D3 addition also potentiated cell differentiation in a concentration- and time-dependent manner, and the enhanced levels of cell differentiation closely correlated with the inhibitory levels of NF-κB-binding activity by costunolide. These results indicate that PKC, PI3-K, ERK and NF-κB may be involved in 1,25-(OH)2D3-mediated cell differentiation enhanced by costunolide.

Original languageEnglish
Pages (from-to)1233-1242
Number of pages10
JournalBiochemical Pharmacology
Volume64
Issue number8
DOIs
Publication statusPublished - 2002 Oct 15
Externally publishedYes

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Keywords

  • 1,25-Dihydroxyvitamin D
  • Cell differentiation
  • Costunolide
  • Extracellular signal-regulated kinase
  • Nuclear factor-κB
  • Protein kinase C

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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