Selective modulation of P-glycoprotein-mediated drug resistance

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Show simple item record Bebawy, M Morris, MB Roufogalis, BD 2012-02-10T06:09:14Z 2001
dc.identifier.citation British Journal of Cancer, 2001, 85 (12), pp. 1998 - 2003
dc.identifier.issn 0007-0920
dc.identifier.other C1UNSUBMIT en_US
dc.description.abstract Multidrug resistance associated with the overexpression of the multidrug transporter P-glycoprotein is a serious impediment to successful cancer treatment. We found that verapamil reversed resistance of CEM/VLB100 cells to vinblastine and fluorescein-colchicine, but not to colchicine. Chlorpromazine reversed resistance to vinblastine but not to fluorescein-colchicine, and it increased resistance to colchicine. Initial influx rates of fluorescein-colchicine were similar in resistant and parental cells, whereas vinblastine uptake was about 10-fold lower in the resistant cells. These results provide indirect evidence that fluorescein-colchicine is transported from the inner leaflet of the membrane and vinblastine from the outer membrane leaflet. Verapamil inhibited fluorescein-colchicine transport in inside-out vesicles made from resistant cells, whilst chlorpromazine was found to activate the transport of fluorescein-colchicine. The chlorpromazine-induced activation of fluorescein-colchicine transport was temperature-dependent and may reflect its interaction with phospholipids localised in the same bilayer leaflet. Conversely, chlorpromazine localisation in this leaflet may be responsible for its allosteric inhibition of vinblastine transport from the opposing membrane leaflet. The proposed relationship between the selectivity of modulation of P-glycoprotein and the membrane localisation of the cytotoxic drug substrates and modulators may have important implications in the rational design of regimes for the circumvention of multidrug resistance clinically. © 2001 Cancer Research Campaign.
dc.language eng
dc.title Selective modulation of P-glycoprotein-mediated drug resistance
dc.type Journal Article
dc.description.version Published
dc.parent British Journal of Cancer
dc.journal.volume 12
dc.journal.volume 85
dc.journal.number 12 en_US
dc.publocation London en_US
dc.identifier.startpage 1998 en_US
dc.identifier.endpage 2003 en_US GSH.Pharmacy en_US
dc.conference Verified OK en_US
dc.for 1112 Oncology and Carcinogenesis
dc.personcode 112474
dc.percentage 100 en_US Oncology and Carcinogenesis en_US
dc.classification.type FOR-08 en_US
dc.edition en_US
dc.custom en_US en_US
dc.location.activity WOS:000173373000026 en_US
dc.description.keywords Chlorpromazine
dc.description.keywords Colchicine
dc.description.keywords Fluorescein-colchicine
dc.description.keywords Multidrug resistance
dc.description.keywords P-glycoprotein
dc.description.keywords Vinblastine
pubs.embargo.period Not known
pubs.organisational-group /University of Technology Sydney
pubs.organisational-group /University of Technology Sydney/Graduate School of Health
pubs.organisational-group /University of Technology Sydney/Strength - Health Technologies
utslib.copyright.status Closed Access 2015-04-15 12:17:09.805752+10
pubs.consider-herdc false
utslib.collection.history Closed (ID: 3)
utslib.collection.history Uncategorised (ID: 363)

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