Document Detail

The hepoxilin analog PBT-3 induces apoptosis in BCR-ABL-positive K562 leukemia cells.
MedLine Citation:
PMID:  14666657     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Leukemia is a heterogeneous disease characterized by malignant proliferation of cells of the hematopoietic system. The use of chemotherapeutic agents is still the mainstay of anti-leukemia therapy. Despite this, significant morbidity and mortality still occurs. We describe herein novel apoptotic effects of PBT-3, one of a family of stable analogs of the Hepoxilins, natural products derived from arachidonic acid. MATERIALS AND METHODS: Inhibition of [3H]-thymidine incorporation, nuclear fragmentation, DNA laddering, FACS analysis as well as Annexin V binding were assessed. RESULTS: PBT-3 dose-dependently causes apoptosis of the CML cell line, K562, in vitro. PBT-3 acts by increasing cytochrome c release into the cytoplasm and by activation of caspase-3 degradation. The effects of PBT-3 compare favorably with those of STI571 (Gleevec), while thromboxane agonists and antagonists are without effect. CONCLUSION: These results suggest that PBT analogs may provide a new platform for the development of apoptotic drugs in leukemia.
Na Qiao; Janice Lam; Denis Reynaud; Mohamed Abdelhaleem; Cecil R Pace-Asciak
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  23     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    2003 Sep-Oct
Date Detail:
Created Date:  2003-12-11     Completed Date:  2004-02-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  3617-22     Citation Subset:  IM    
Research Institute and Division of Haematopathology, Hospital for Sick Children, 555 University Avenue, Toronto, M5G 1X8, Canada.
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MeSH Terms
8,11,14-Eicosatrienoic Acid / analogs & derivatives*,  pharmacology*
Apoptosis / drug effects*
Caspase 3
Caspases / metabolism
Cell Division / drug effects
Cytochromes c / secretion
Fusion Proteins, bcr-abl / metabolism
K562 Cells
Receptors, Thromboxane / metabolism
Reg. No./Substance:
0/Fusion Proteins, bcr-abl; 0/PBT-3 compound; 0/Receptors, Thromboxane; 7324-41-6/8,11,14-Eicosatrienoic Acid; 9007-43-6/Cytochromes c; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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