Abstract
We demonstrate that decursin induces apoptosis via regulation of cyclooxygenase-2 (COX-2) and survivin in leukemic KBM-5 cells. By activating an apoptotic machinery, decursin is cytotoxic to KBM-5 cells. In this apoptotic process, decursin can activate caspase family members and triggers PARP cleavage. At the same time, the expression of COX-2 and survivin in the cells is downregulated. Furthermore, decursin is in synergy with COX-2 inhibitor, celecoxib or NS398 for the induction of apoptosis. Overall, these results suggest that decursin, via inhibiting COX-2 and survivin, sensitizes human leukemia cells to apoptosis and is a potential chemotherapeutic agent to treat this disease.
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects*
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Benzopyrans / chemistry
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Benzopyrans / pharmacology*
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Blotting, Western
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Butyrates / chemistry
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Butyrates / pharmacology*
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Caspase 3 / metabolism
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Caspase 9 / metabolism
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Cell Cycle / drug effects
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Cell Line, Tumor
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Cell Survival / drug effects
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Cyclooxygenase 2 / genetics
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Cyclooxygenase 2 / metabolism*
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Dose-Response Relationship, Drug
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Enzyme Activation / drug effects
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Flow Cytometry
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HL-60 Cells
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Humans
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In Situ Nick-End Labeling
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Inhibitor of Apoptosis Proteins
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Leukemia, Myeloid / metabolism
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Leukemia, Myeloid / pathology
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Lymphocytes / cytology
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Lymphocytes / drug effects
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Lymphocytes / metabolism
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Microtubule-Associated Proteins / metabolism*
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Molecular Structure
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Poly(ADP-ribose) Polymerases / metabolism
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Protein Kinase C / metabolism
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Signal Transduction / drug effects
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Survivin
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U937 Cells
Substances
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BIRC5 protein, human
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Benzopyrans
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Butyrates
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Inhibitor of Apoptosis Proteins
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Microtubule-Associated Proteins
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Survivin
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decursin
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Cyclooxygenase 2
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Poly(ADP-ribose) Polymerases
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Protein Kinase C
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Caspase 3
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Caspase 9