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 language | English |
---|---|
Pages (from-to) | 223-229 |
Number of pages | 7 |
Journal | Planta Medica |
Volume | 69 |
Issue number | 3 |
DOIs | |
Publication status | Published - 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