Document Detail


Cytosine arabinoside induces programmed endothelial cell death through the caspase-3 pathway.
MedLine Citation:
PMID:  16581899     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The anti-cancer effects of cytosine arabinoside (ARA-C) are well known. However, effects on nonmalignant cells have not been elucidated and may be important to understanding treatment-related toxicity. The purpose of this study was to examine the effect of ARA-C on nondividing vascular endothelial cells. The objectives were to determine the effects of ARA-C on cell viability and to ascertain whether ARA-C caused apoptosis in cultured vascular endothelial cells and hydrocortisone blunted caspase-3-induced apoptosis. Endothelial cells were cultured until confluent and mitotically quiescent then exposed to ARA-C (10(-7)to 10(-3) M) for 1 to 4 days. Some experiments involved cotreatment with hydrocortisone (10(-11),10(-10),10(-4), and 10(-3) M). Light microscopy and the colorimetric MTS assay were used to measure viability. Fluorescent annexin-V and DNA fragmentation assays were used to measure apoptosis, and a fluorescence-based enzymatic assay was used to measure caspase-3 activity, which is one pathway involved in the apoptosis cascade. Two-way ANOVA or the appropriate nonparametric test was used to determine statistical significance in studies of viability and apoptosis. Oneway ANOVA was used to determine statistical significance for caspase-3 activity. Viability was decreased with higher concentrations of ARA-C and increased days of treatment. The percentage of apoptotic cells increased with higher concentrations of ARA-C and increased days of treatment. ARA-C-treated samples showed DNA fragmentation, indicative of apoptosis. Caspase-3 activity increased after ARA-C addition; hydrocortisone blunted this increase. ARA-C caused apoptosis in nondividing endothelial cells in culture. Hydrocortisone may protect against ARA-C-induced apoptosis by reducing caspase-3 activity.
Authors:
Ida M Ki Moore; Carrie J Merkle; Petra Miketova; Renee K Salyer; Bonny J Torres; Richard C Schaeffer; David W Montgomery
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biological research for nursing     Volume:  7     ISSN:  1099-8004     ISO Abbreviation:  Biol Res Nurs     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-04-03     Completed Date:  2006-05-11     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9815758     Medline TA:  Biol Res Nurs     Country:  United States    
Other Details:
Languages:  eng     Pagination:  289-96     Citation Subset:  IM; N    
Affiliation:
College of Nursing, University of Arizona, Tucson 85721-0203, USA. kmoore@nursing.arizona.edu
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Anti-Inflammatory Agents / pharmacology
Antimetabolites, Antineoplastic / adverse effects*
Apoptosis / drug effects*,  physiology
Caspase 3
Caspases / drug effects*,  physiology
Cattle
Cell Survival / drug effects
Cells, Cultured
Cognition Disorders / chemically induced
Colorimetry
Cytarabine / adverse effects*
DNA Fragmentation
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Endothelium, Vascular* / cytology,  drug effects
Humans
Hydrocortisone / pharmacology
Microscopy, Fluorescence
Microscopy, Polarization
Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
Statistics, Nonparametric
Grant Support
ID/Acronym/Agency:
NR004343/NR/NINR NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Antimetabolites, Antineoplastic; 147-94-4/Cytarabine; 50-23-7/Hydrocortisone; 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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