Document Detail

The effect of 3-(5-nitro-2-thienyl)-9-chloro-5-morpholin-4-yl[1,2,4]triazolo[4,3-c]quinazoline on cell growth, cell cycle, induction of DNA fragmentation, and activity of caspase 3 in murine leukemia L1210 cells and fibroblast NIH-3T3 cells.
MedLine Citation:
PMID:  16342136     Owner:  NLM     Status:  MEDLINE    
Quinazolines are multitarget agents, which have broad spectrum of biological activity, and some of them are now in cancer clinical testing. 3-(5-nitro-2-thienyl)-9-chloro-5-morpholin-4-yl[1,2,4]triazolo[4,3-c]quinazoline is a new synthetically prepared derivative, which in our previous study showed cytotoxic effects on cancer cell lines HeLa and B16. Quinazoline, at micromolar concentrations, induced morphological changes and necrosis of B16 cells, and at nanomolar concentrations it produced changes of F-actin cytoskeleton. It did not cause changes in the cell cycle, did not induce apoptotic cell death in B16 cells, did not have a mutagenic effect, and did not even behave as a typical intercalating agent. Little significant reduction of tumor volume in intramuscular transplanted B16 cells was observed. The aim of the present study was to examine the cytotoxic effect of 3-(5-nitro-2-thienyl)-9-chloro-5-morpholin-4-yl[1,2,4]triazolo[4,3-c]quinazoline on murine leukemia L1210 cells and fibroblast NIH-3T3 cells. Induction of cell morphology and cell cycle changes, induction of apoptosis and caspase 3 activity were studied. Quinazoline acted cytotoxically on both cell lines. The sensitivity of leukemia L1210 cells to the quinazoline was higher than that of fibroblast NIH-3T3. The IC(100) was 12 microM for L1210 cells and 24 microM for NIH-3T3 cells. No effect of quinazoline on the cell cycle profile of L1210 and NIH-3T3 was detected, however, quinazoline induced an increase of the sub-G(0) cell fraction, apoptotic DNA fragmentation, and apoptotic morphological changes at a concentration of 12 microM. This quinazoline concentration induced caspase 3 activity. Our results demonstrated that induction of apoptotic cell death via activation of caspase 3 contributed to the cytotoxic effects of 3-(5-nitro-2-thienyl)-9-chloro-5-morpholin-4-yl[1,2,4]triazolo[4,3-c]quinazoline in murine leukemia L1210 cells.
S Jantová; S Letasiová; A Repický; R Ovádeková; B Lakatos
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell biochemistry and function     Volume:  24     ISSN:  0263-6484     ISO Abbreviation:  Cell Biochem. Funct.     Publication Date:    2006 Nov-Dec
Date Detail:
Created Date:  2006-10-25     Completed Date:  2007-02-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8305874     Medline TA:  Cell Biochem Funct     Country:  England    
Other Details:
Languages:  eng     Pagination:  519-30     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2005 John Wiley & Sons, Ltd.
Department of Biochemistry and Microbiology, Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinského 9, SK-81237 Bratislava, Slovak Republic.
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MeSH Terms
Apoptosis / drug effects*
Caspase 3 / metabolism*
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
DNA Fragmentation / drug effects*
Dose-Response Relationship, Drug
Enzyme Activation / drug effects
Fibroblasts / drug effects*,  metabolism
Molecular Structure
NIH 3T3 Cells
Quinazolines / chemistry,  pharmacology*
Time Factors
Triazoles / chemistry,  pharmacology*
Reg. No./Substance:
0/3-(5-nitro-2-thienyl)-9-chloro-5-morpholin-4-yl(1,2,4)triazolo(4,3-c)quinazoline; 0/Quinazolines; 0/Triazoles; EC 3.4.22.-/Caspase 3

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