Source:http://linkedlifedata.com/resource/pubmed/id/12677525
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2003-4-4
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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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Plant Preparations,
http://linkedlifedata.com/resource/pubmed/chemical/Pyranocoumarins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0032-0943
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
69
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
223-9
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pubmed:dateRevised |
2006-11-15
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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
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pubmed:year |
2003
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pubmed:articleTitle |
Pyranocoumarins isolated from Peucedanum praeruptorum as differentiation inducers in human leukemic HL-60 cells.
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pubmed:affiliation |
Bioactive Products Research Group, City University of Hong Kong, Kowloon, Hong Kong SAR, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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