Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-4-4
pubmed:abstractText
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 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0032-0943
pubmed:author
pubmed:issnType
Print
pubmed:volume
69
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
223-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12677525-Antineoplastic Agents, Phytogenic, pubmed-meshheading:12677525-Apiaceae, pubmed-meshheading:12677525-Blotting, Western, pubmed-meshheading:12677525-Cell Cycle, pubmed-meshheading:12677525-Cell Cycle Proteins, pubmed-meshheading:12677525-Cell Differentiation, pubmed-meshheading:12677525-Cyclin-Dependent Kinase Inhibitor p27, pubmed-meshheading:12677525-Dose-Response Relationship, Drug, pubmed-meshheading:12677525-Flow Cytometry, pubmed-meshheading:12677525-Gene Expression Regulation, Leukemic, pubmed-meshheading:12677525-HL-60 Cells, pubmed-meshheading:12677525-Humans, pubmed-meshheading:12677525-Leukemia, Myeloid, pubmed-meshheading:12677525-Phytotherapy, pubmed-meshheading:12677525-Plant Preparations, pubmed-meshheading:12677525-Pyranocoumarins, pubmed-meshheading:12677525-Tumor Suppressor Proteins
pubmed:year
2003
pubmed:articleTitle
Pyranocoumarins isolated from Peucedanum praeruptorum as differentiation inducers in human leukemic HL-60 cells.
pubmed:affiliation
Bioactive Products Research Group, City University of Hong Kong, Kowloon, Hong Kong SAR, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't