Linked Life Data

1363515

Source:http://linkedlifedata.com/resource/pubmed/id/1363515

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6B
pubmed:dateCreated
1993-4-9
pubmed:abstractText
Cyclosporin A and verapamil are substrates for P-glycoprotein. Both agents are known to reverse multidrug resistance in cells overexpressing P-glycoprotein. In this investigation, we have examined the effects of cyclosporin A and verapamil on multidrug resistance in HL60/AR cells that lack P-glycoprotein. In addition, a correlation was sought between an alteration in plasma membrane potential as measured with cationic dye DIOC5 and overexpression of P-glycoprotein. HL60/AR cells accumulated 3 fold less daunorubicin than HL60 cells. The drug accumulation defect and drug resistance in HL60/AR cells were partially corrected by verapamil and buthionine sulfoximine. However, cyclosporin A had no detectable effect on daunorubicin accumulation or drug resistance in HL60/AR cells. The multidrug resistant P338/ADR cell line overexpressed P-glycoprotein and exhibited depolarization of plasma membrane when compared to its corresponding drug sensitive parental cell line. In contrast, HL60/AR cells lacked P-glycoprotein and plasma membrane potentials were similar to those of drug sensitive HL60 cells. These results suggest that [1] verapamil modulates daunorubicin transport by a mechanism independent of P-glycoprotein, [2] the mechanisms of reversal of multidrug resistance by verapamil and cyclosporin A are distinct, and [3] the plasma membrane depolarization in multidrug resistant cell lines that overexpress P-glycoprotein, as determined by DIOC5, may be due to an increased efflux of cationic dye by P-glycoprotein, rather than a true measurement of plasma membrane potential in multidrug resistant cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0250-7005
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2127-32
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:articleTitle
Lack of reversal of daunorubicin resistance in HL60/AR cells by cyclosporin A.
pubmed:affiliation
Division of Basic and Clinical Immunology, University of California, Irvine 92717.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.