Tamoxifen decreases drug efflux from liposomes: relevance to its ability to reverse multidrug resistance in cancer cells?
Tamoxifen decreased the efflux of the fluorescent marker drug, chloroquine, from phosphatidylcholine liposomes. Tamoxifen is a known structural-mimic of cholesterol, which were both found to be similarly effective in preventing drug release from liposomes. This ability of tamoxifen and cholesterol to decrease drug efflux in a concentration-dependent manner is likely to arise from their known ability to decrease membrane fluidity both in liposomes and also in cancer cells. The possible importance of the ability of tamoxifen to inhibit drug efflux from liposomes in relation to its ability to reverse multidrug resistance in cancer patients caused by the efflux of cytotoxic therapeutic agents, is discussed.
Kayyali
R
R
Department of Pharmacy, King's College, London, UK.
Marriott
C
C
Wiseman
H
H
D000970:Antineoplastic Agents / Q000378:metabolism; D002738:Chloroquine / Q000378:metabolism*; D002784:Cholesterol / Q000494:pharmacology; D004351:Drug Resistance; D006801:Humans; D007700:Kinetics; D008081:Liposomes / Q000378:metabolism*; D008560:Membrane Fluidity / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy*; D010713:Phosphatidylcholines / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*
D000970:Antineoplastic Agents; D008081:Liposomes; D010713:Phosphatidylcholines; D013629:Tamoxifen; D002738:Chloroquine; D002784:Cholesterol