Pyranocoumarins isolated from Peucedanum praeruptorum as differentiation inducers in human leukemic HL-60 cells

Jin Xia Zhang, David W F FONG*, Jimmy Yiu-Cheong Wu, Mengsu Yang, Hon Yeung Cheung

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

Differentiation therapy for myeloid leukemia offers great potential as a supplement to the current treatment modalities. In the present report, we investigated if the pyranocoumarins, (±)-4′-O-acetyl-3′-O-angeloyl-cis-khellactone (or angular pyranocoumarin, APC) isolated from the medicinal plant Peucedanum praeruptorum Dunn, could induce human acute myeloid leukemic HL-60 cells to differentiate and elucidated the molecular mechanism(s) involved. The ability of HL-60 cells to reduce nitroblue tetrazolium (NBT) was significantly increased after APC treatment for 72 h. In these differentiating HL-60 cells, cell surface differentiation markers CD11b (for myeloid cells) and CD14 (for monocytic cells) were detected in 90.3% and 70.1% of the cells, respectively. The differentiation inducing effect of APC was time- and dose-dependent. Treatment with 20 μg/mL APC for 72 h inhibited cell growth by 90% and cell cycle analysis revealed an increase in the proportion of G1 phase cells. In these growth-inhibited cells the expression of the cyclin-dependent kinase inhibitor p27kip1, but not p21WAF1, was up-regulated as shown by Western blotting. Differentiation inducing signal pathways were investigated and it was shown that phospho-MEK and phospho-ERK were elevated shortly after the addition of APC. Pre-incubation of the cells with MEK1 inhibitor PD98059 blocked this APC-induced differentiation. Our results suggest that APC are potent inducers of HL-60 cell differentiation along both the myelocytic and monocytic lineages and are potential agents for differentiation-treatment of leukemia.

Original languageEnglish
Pages (from-to)223-229
Number of pages7
JournalPlanta Medica
Volume69
Issue number3
DOIs
Publication statusPublished - 1 Mar 2003

Scopus Subject Areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

User-Defined Keywords

  • Apiaceae
  • Differentiation
  • HL-60
  • MEK/ERK pathways
  • p27
  • Peucedanum praeruptorum
  • Pyranocoumarins

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