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pubmed-article:12677525pubmed:abstractTextDifferentiation 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 microg/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 p27 kip1, but not p21 WAF1, 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.lld:pubmed
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pubmed-article:12677525pubmed:authorpubmed-author:YangMengsuMlld:pubmed
pubmed-article:12677525pubmed:authorpubmed-author:FongWang-FunW...lld:pubmed
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pubmed-article:12677525pubmed:pagination223-9lld:pubmed
pubmed-article:12677525pubmed:dateRevised2006-11-15lld:pubmed
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pubmed-article:12677525pubmed:articleTitlePyranocoumarins isolated from Peucedanum praeruptorum as differentiation inducers in human leukemic HL-60 cells.lld:pubmed
pubmed-article:12677525pubmed:affiliationBioactive Products Research Group, City University of Hong Kong, Kowloon, Hong Kong SAR, China.lld:pubmed
pubmed-article:12677525pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:12677525pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed