Document Detail

Butyrate-stable monosaccharide derivatives induce maturation and apoptosis in human acute myeloid leukaemia cells.
MedLine Citation:
PMID:  9633898     Owner:  NLM     Status:  MEDLINE    
The rapid degradation and subsequent lack of efficacy of n-butyric acid in vivo has been improved by the synthesis of monosaccharide stable pro-drugs of butyric acid. We studied the effects of D1 (O-n-butanoyl-2,3-O-isopropylidene-alpha-D-mannofuranoside), G1 (1-O-n-butanoyl-D,L-xylitol), and F1 (1-O-n-butanoyl 2,3-O-isopropylidene-D,L-xylitol) on the maturation and proliferation of AML cell lines HL 60 and FLG 29.1 and of purified blast cells from 10 cases of de novo acute myeloid leukaemia (AML). AML cell maturation was measured by surface antigen expression, morphology and cytochemistry. Toxicology in mice was also evaluated (DL50 1000 mg/kg). In HL 60 cells G1 and D1 increased the expression of CD15 and CD11a (presenting 62% of promyelo-metamyelocytes), and in 7/10 cases of primary AMLs that of CD11a, CD11b, CD15, and myeloperoxidase. D1, G1 and F1 induced a dose-dependent inhibition of tritiated thymidine uptake. Apoptosis (evaluated by flow cytometry and agarose gel electrophoresis) was induced in AML blasts by D1 and F1 (79% and 94% respectively for HL 60 cells) and, with less effect, by G1 (27%). The persistence of maturative and apoptotic activity in these new pro-drugs of butyric acid, hydrolysed only inside the tumour cell, suggests a possible use in differentiation therapy of myelodysplastic syndromes and AMLs.
V Santini; B Scappini; A Gozzini; A Grossi; P Villa; G Ronco; O Douillet; P Pouillart; P A Bernabei; P Rossi Ferrini
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of haematology     Volume:  101     ISSN:  0007-1048     ISO Abbreviation:  Br. J. Haematol.     Publication Date:  1998 Jun 
Date Detail:
Created Date:  1998-07-31     Completed Date:  1998-07-31     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372544     Medline TA:  Br J Haematol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  529-38     Citation Subset:  IM    
Department of Haematology, University of Florence, Italy.
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MeSH Terms
Acute Disease
Apoptosis / drug effects*
Butyric Acid
Butyric Acids / pharmacology*,  toxicity
Cell Division / drug effects
DNA / analysis
DNA Fragmentation
HL-60 Cells
Leukemia, Myeloid / metabolism,  pathology*
Monosaccharides / pharmacology
Thymidine / metabolism
Tumor Cells, Cultured
Reg. No./Substance:
0/Butyric Acids; 0/Monosaccharides; 107-92-6/Butyric Acid; 50-89-5/Thymidine; 9007-49-2/DNA

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