Document Detail

KRN5500, a novel antitumor agent, induces apoptosis or cell differentiation in HL-60 cells.
MedLine Citation:
PMID:  10685078     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: KRN5500, a derivative of spicamycin, shows antitumor activity against a variety of tumor cell lines. However, the mechanism of cytotoxic action has remained unclear. METHODS: The viability of HL-60 human leukemic cells treated with KRN5500 was studied by the dye exclusion assay. Induction of apoptosis and effects on the cell cycle were investigated by flow cytometry: We measured cellular DNA content after extraction of fragmented DNA, and apoptosis-induced DNA strand breaks. Cell morphology was observed by light microscopy. DNA strand breaks at a nucleosomal unit were analyzed by electrophoresis. RESULTS: Our data demonstrated that KRN5500 caused inhibition of cell growth, and that apoptosis was the mode of cell death. G(1) phase cells were more susceptible to KRN5500 induced apoptosis. In addition, KRN5500 induced cell differentiation at lower concentration. CONCLUSIONS: It is anticipated that KRN5500 will be used clinically as an anti-leukemic agent. Its mechanism of antitumor action is to induce apoptosis or cell differentiation.
K Kawasaki; T Murakami; M Ita; K Sasaki; S Furukawa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cytometry     Volume:  39     ISSN:  0196-4763     ISO Abbreviation:  Cytometry     Publication Date:  2000 Mar 
Date Detail:
Created Date:  2000-04-05     Completed Date:  2000-04-05     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  8102328     Medline TA:  Cytometry     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  211-6     Citation Subset:  IM    
Copyright Information:
Copyright 2000 Wiley-Liss, Inc.
Department of Pediatrics, Yamaguchi University School of Medicine, Ube, Japan.
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MeSH Terms
Antibiotics, Antineoplastic / toxicity*
Apoptosis / drug effects*
Cell Differentiation / drug effects*
Cell Survival / drug effects
Cells, Cultured
DNA, Neoplasm / isolation & purification
Flow Cytometry / methods
HL-60 Cells
Lymphocytes / cytology,  drug effects*
Purine Nucleosides / toxicity
Time Factors
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/DNA, Neoplasm; 0/KRN 5500; 0/Purine Nucleosides

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