ArticleIn vitro cellular & developmental biology. Animal
Effect of the modulation of the membrane lipid composition on the localization and function of P-glycoprotein in MDR1-MDCK cells.
Article in In vitro cellular & developmental biology. Animal. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 58 citations in OpenAlex.
- Polyphyllin H Reverses Paclitaxel Resistance in Breast Cancer by Binding Membrane Cholesterol to Inhibit Both ABCB1 and ABCC3.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Cholesterol-Depletion-Induced Membrane Repair Carries a Raft Conformer of P-Glycoprotein to the Cell Surface, Indicating Enhanced Cholesterol Trafficking in MDR Cells, Which Makes Them Resistant to Cholesterol Modifications.International journal of molecular sciences · 2023Article
- Regulation of Drug Transport Proteins-From Mechanisms to Clinical Impact: A White Paper on Behalf of the International Transporter Consortium.Clinical pharmacology and therapeutics · 2022Review
- Interaction of Commonly Used Oral Molecular Excipients with P-glycoprotein.The AAPS journal · 2021Article
- microRNAs targeting cellular cholesterol: implications for combating anticancer drug resistance.Genes & cancer · 2020Article
- Lipoproteins modulate growth and P-glycoprotein expression in drug-resistant HER2-overexpressed breast cancer cells.Heliyon · 2019Article
- Phase Composition Control in Microsphere-Supported Biomembrane Systems.Langmuir : the ACS journal of surfaces and colloids · 2017Article
- Pluronics and MDR reversal: an update.Molecular pharmaceutics · 2014Review
- Complex Interplay between the P-Glycoprotein Multidrug Efflux Pump and the Membrane: Its Role in Modulating Protein Function.Frontiers in oncology · 2014Review
- Effect of sesquiterpene lactone coronopilin on leukaemia cell population growth, cell type-specific induction of apoptosis and mitotic catastrophe.Cell proliferation · 2012Article
- Methotrexate-loaded chitosan- and glycol chitosan-based nanoparticles: a promising strategy for the administration of the anticancer drug to brain tumors.AAPS PharmSciTech · 2011Article
- Glycosphingolipid functions.Cold Spring Harbor perspectives in biology · 2011Review
- Review
- P-glycoprotein in proteoliposomes with low residual detergent: the effects of cholesterol.Pharmaceutical research · 2007Article
- Assessing the nature of lipid raft membranes.PLoS computational biology · 2007Article
- Preface: the concept and consequences of multidrug resistance.Pflugers Archiv : European journal of physiology · 2007Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multidrug resistance (MDR) is a major obstacle in cancer therapy. It results from different mechanisms; among them is P-glycoprotein (P-gp)-mediated drug efflux out of cells. The mechanism of action remains elusive. The membrane lipid surrounding of P-gp, especially cholesterol, has been postulated to play an important role. To determine the effect of cholesterol depletion on P-gp, Madin Darby canine kidney (MDCK) cells, transfected with the mdr1 gene (MDR1-MDCK cells), were treated with methyl-beta-cyclodextrin (MbetaCD). The localization and function of P-gp were analyzed using confocal laser scanning microscopy. Treatment with 100 mM MbetaCD did not affect viability but altered the structural appearance of the cells and abolished efflux of rhodamine 123, a P-gp substrate. The MbetaCD treatment released P-gp from intact cells into the supernatant and reduced the amount of P-gp in total membrane preparations. The P-gp was shifted from the raft fractions (1% Triton X-100, 4 degrees C) to higher density fractions in MbetaCD-treated cells. The amount of cholesterol was significantly decreased in the raft fractions. Treatment of cells with 1-phenyl-2-decanoylamino-3-morpholino-1-propanol, a glucosylceramide synthase inhibitor, also led to a shift of P-gp to higher density fractions. These results show that removal of cholesterol modulates the membrane lipid composition, changes the localization of P-gp, and results in loss of P-gp function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.