Document Detail


Vinorelbine induces apoptosis and caspase-3 (CPP32) expression in leukemia and lymphoma cells: a comparison with vincristine.
MedLine Citation:
PMID:  9720729     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Vinorelbine (NVB) is a novel vinca alkaloid FDA approved for use in some advanced carcinomas. However, its role in non-Hodgkin's lymphoma (NHL) is still not well defined. NVB is an antimicrotubule agent, but as yet, it is not known whether it induces apoptosis. By flow cytometry using nuclear staining (propidium iodide) and annexin V, we demonstrated that NVB and vincristine (VCR) induced both mitotic arrest and apoptosis in leukemia and lymphoma cells, in a drug exposure time dependent manner. Cell cycle kinetics in 3 different cell lines varied during vinca alkaloid treatment. The annexin V method showed that apoptosis, as opposed to necrosis, was the dominant mode of cell kill of chemosensitive leukemia and lymphoma cells. Phosphatidylserine expression on the cell surface was detectable as a hallmark of apoptosis at earlier drug exposure when compared to conventional flow cytometry with PI staining. By Western blot analysis, we demonstrated that CPP32 or caspase-3, a critical apoptosis inducer, and its active subunits p20 and p11 were upregulated in chemo- and apoptosis-sensitive lymphoma and leukemia cells treated with NVB. Our data contributes to the emerging hypothesis suggesting that widely divergent exogenous stimuli and chemotherapeutic agents can effect apoptosis in cancer cells via different pathways involving the caspases. We believe that vinorelbine may be a potentially important drug in the treatment of NHL in the future.
Authors:
H C Toh; L Sun; C H Koh; S E Aw
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Leukemia & lymphoma     Volume:  31     ISSN:  1042-8194     ISO Abbreviation:  Leuk. Lymphoma     Publication Date:  1998 Sep 
Date Detail:
Created Date:  1998-11-17     Completed Date:  1998-11-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9007422     Medline TA:  Leuk Lymphoma     Country:  SWITZERLAND    
Other Details:
Languages:  eng     Pagination:  195-208     Citation Subset:  IM    
Affiliation:
Department of Medical Oncology, Singapore General Hospital, Singapore. HCToh@att.net
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MeSH Terms
Descriptor/Qualifier:
Annexin A5 / analysis
Antineoplastic Agents, Phytogenic / therapeutic use*
Apoptosis / drug effects*
Burkitt Lymphoma / drug therapy*,  pathology
Caspase 3
Caspases / biosynthesis*
Cell Cycle / drug effects
Enzyme Induction
Flow Cytometry
Humans
Leukemia, T-Cell / drug therapy*,  pathology
Tumor Cells, Cultured
Vinblastine / analogs & derivatives*,  therapeutic use
Vincristine / therapeutic use*
Chemical
Reg. No./Substance:
0/Annexin A5; 0/Antineoplastic Agents, Phytogenic; 57-22-7/Vincristine; 71486-22-1/vinorelbine; 865-21-4/Vinblastine; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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