Linked Life Data

10329417

Source:http://linkedlifedata.com/resource/pubmed/id/10329417

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-6-24
pubmed:abstractText
Multidrug resistance-associated protein (MRP) and P-glycoprotein (P-gp) are drug efflux pumps conferring multidrug resistance to tumor cells. RU486, an antiprogestatin drug known to inhibit P-gp function, was examined for its effect on MRP activity in MRP-overexpressing lung tumor GLC4/Sb30 cells. In such cells, the antihormone compound was found to increase intracellular accumulation of calcein, a fluorescent compound transported by MRP, in a dose-dependent manner, through inhibition of cellular export of the dye; in contrast, it did not alter calcein levels in parental GLC4 cells. RU486, when used at 10 microM, a concentration close to plasma concentrations achievable in humans, strongly enhanced the sensitivity of GLC4/Sb30 cells towards two known cytotoxic substrates of MRP, the anticancer drug vincristine and the heavy metal salt potassium antimonyl tartrate. Vincristine accumulation levels were moreover up-regulated in RU486-treated GLC4/Sb30 cells. In addition, such cells were demonstrated to display reduced cellular levels of glutathione which is required for MRP-mediated transport of some anticancer drugs. These findings therefore demonstrate that RU486 can down-modulate MRP-mediated drug resistance, in addition to that linked to P-gp, through inhibition of MRP function.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-291X
pubmed:author
pubmed:copyrightInfo
Copyright 1999 Academic Press.
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
258
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
513-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Reversal of MRP-mediated multidrug resistance in human lung cancer cells by the antiprogestatin drug RU486.
pubmed:affiliation
Unité INSERM U456 Détoxication et Réparation Tissulaire, Faculté des Sciences Pharmaceutiques et Biologiques, 2 Avenue du Pr L. Bernard, Rennes, 35043, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't