Document Detail


Gallic acid inhibits ribonucleotide reductase and cyclooxygenases in human HL-60 promyelocytic leukemia cells.
MedLine Citation:
PMID:  16488533     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Gallic acid (GA) is a naturally occurring polyhydroxyphenolic compound and an excellent free radical scavenger. In this study, we examined its cytotoxic and biochemical effects on the human HL-60 promyelocytic leukemia cell line. GA caused a significant imbalance of deoxynucleosidetriphosphate (dNTP) pool sizes, indicating ribonucleotide reductase inhibition. Moreover, GA induced dose-dependent apoptosis in HL-60 cells (80microM GA led to the induction of apoptosis in 39% of cells) and attenuated progression from G0/G1 to the S phase of the cell cycle (60microM GA doubled the number of cells in G0/G1 phase from 22 to 44% when compared to untreated controls). We further determined IC(50) values of 3.5 and 4.4nM for the inhibition of cyclooxygenases I and II, respectively. When cells were simultaneously treated with GA and trimidox, another inhibitor of RR, highly synergistic growth inhibitory effects could be observed. Taken together, we identified novel biochemical effects of GA which could be the basis for further preclinical and in vivo studies.
Authors:
Sibylle Madlener; Christoph Illmer; Zsuzsanna Horvath; Philipp Saiko; Annemarie Losert; Irene Herbacek; Michael Grusch; Howard L Elford; Georg Krupitza; Astrid Bernhaus; Monika Fritzer-Szekeres; Thomas Szekeres
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Publication Detail:
Type:  Journal Article     Date:  2006-02-20
Journal Detail:
Title:  Cancer letters     Volume:  245     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2006-12-25     Completed Date:  2007-04-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  156-62     Citation Subset:  IM    
Affiliation:
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, General Hospital of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Apoptosis / drug effects
Benzamidines / chemistry,  pharmacology
Cell Cycle / drug effects
Cell Proliferation / drug effects
Cell Survival / drug effects
Cyclooxygenase Inhibitors / pharmacology*
Cytidine Triphosphate / metabolism
Dose-Response Relationship, Drug
Enzyme Inhibitors / chemistry,  pharmacology
Gallic Acid / chemistry,  pharmacology*
Guanosine Triphosphate / metabolism
HL-60 Cells
Humans
Leukemia, Promyelocytic, Acute / enzymology,  metabolism,  pathology
Molecular Structure
Prostaglandin-Endoperoxide Synthases / metabolism*
Ribonucleotide Reductases / antagonists & inhibitors*,  metabolism
Thymine Nucleotides / metabolism
Chemical
Reg. No./Substance:
0/3,4,5-trihydroxybenzamidoxime; 0/Benzamidines; 0/Cyclooxygenase Inhibitors; 0/Enzyme Inhibitors; 0/Thymine Nucleotides; 149-91-7/Gallic Acid; 365-08-2/thymidine 5'-triphosphate; 56-65-5/Adenosine Triphosphate; 65-47-4/Cytidine Triphosphate; 86-01-1/Guanosine Triphosphate; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases; EC 1.17.4.-/Ribonucleotide Reductases

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


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