Linked Life Data

2032209

Source:http://linkedlifedata.com/resource/pubmed/id/2032209

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1991-6-26
pubmed:abstractText
Cyclosporin A has been reported to enhance the sensitivity of cells displaying multiple drug resistance to anthracyclines. However, the mechanism of action of cyclosporin A in modulating drug resistance is still controversial. This study compares the effects of cyclosporin A and verapamil on doxorubicin resistance in chinese hamster ovary cells (CHRC5) using several criteria including in vitro cytotoxicity, drug accumulation, intracellular distribution by video microscopy, and nuclear DNA damage. Our results demonstrate that verapamil modulation of doxorubicin resistance was paralleled by cellular accumulation of doxorubicin, altered intracellular distribution of doxorubicin from cytoplasm to nucleus, and an increase in the formation of doxorubicin related DNA strand breaks. In contrast, the modulating effect of cyclosporin was qualitatively different. High concentrations of cyclosporin (5 micrograms/ml) increased doxorubicin accumulation and caused partial redistribution to the nucleus. However, with low concentrations of cyclosporin (1 microgram/ml) increased doxorubicin sensitivity was observed without changes in net accumulation of doxorubicin or intracellular distribution, and without enhanced doxorubicin induced DNA breakage. These results suggest that cyclosporin A can modulate doxorubicin cytotoxicity by means other than interference with the P-glycoprotein drug efflux system.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0304-3835
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
57
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
209-18
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Verapamil and cyclosporin A modulate doxorubicin toxicity by distinct mechanisms.
pubmed:affiliation
Department of Pharmacology, Lineberger Cancer Research Center, University of North Carolina, Chapel Hill 27599.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.