scholarly journals Lectin detection of cell surface saccharides remodeling induced by development of P-glycoprotein mediated multidrug resistance phenotype in L1210 leukemia cells

2014 ◽  
Vol 7 (1) ◽  
pp. 52-56 ◽  
Author(s):  
Mário Šereš ◽  
Lucia Pavlíková ◽  
Zdena Sulová ◽  
Albert Breier
Keyword(s):  
Multidrug Resistance ◽  
Cell Surface ◽  
Efflux Pump ◽  
L1210 Cell ◽  
Leukemia Cells ◽  
Drug Efflux ◽  
L1210 Leukemia ◽  
P Glycoprotein ◽  
Drug Efflux Pump ◽  
State Of Art

Abstract P-glycoprotein is an ATP dependent drug efflux pump the expression of which is responsible for strong depression of cell sensitivities to large group of structurally unrelated substances in neoplastic cells. We found that the expression of this protein in mice leukemia cells L1210 is associated with massive remodeling of cell surface saccharides. This remodeling is consistent with the alteration of cellular contents of UDP-sugars, glycogen and glycoproteins when P-gp positive and P-gp negative L1210 cell variants were compared. The current paper is focused on bringing the state of art information about this topic.

Human hepatocellular carcinoma cell lines exhibit multidrug resistance unrelated to MRD1 gene expression

1991 ◽  
Vol 98 (3) ◽  
pp. 317-322
Author(s):  
D.W. Shen ◽  
Y.G. Lu ◽  
K.V. Chin ◽  
I. Pastan ◽  
M.M. Gottesman
Keyword(s):  
Hepatocellular Carcinoma ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Cell Lines ◽  
Actinomycin D ◽  
Efflux Pump ◽  
Mdr1 Gene ◽  
Drug Efflux ◽  
P Glycoprotein ◽  
Drug Efflux Pump

Multidrug resistance of human cancer cells may result from expression of P-glycoprotein, the product of the MRD1 gene, acting as an energy-dependent drug efflux pump. However, direct evidence that expression of the MDR1 gene contributes to the multidrug resistance of human liver carcinomas has not been established. In this study, we tested five cell lines derived from human hepatocellular carcinomas for sensitivity to a variety of drugs used widely as anticancer agents; these included vinblastine, doxorubicin, actinomycin D, mitomycin C, 5-fluorouracil, 6-mercaptopurine, melphalan, methotrexate, cis-platinum and etoposide (VP-16). All five hepatoma cell lines were resistant at different levels to these chemicals compared to human KB cells. Although it has been demonstrated that resistance to vinblastine, colchicine, doxorubicin and actinomycin D in human multidrug-resistant cells is associated with overexpression of P-glycoprotein, very little expression of P-glycoprotein was found in these human hepatoma cells. Neither verapamil nor quinidine, inhibitors of the drug efflux pump, were able to overcome multidrug resistance in hepatoma cells. These results indicate that the multidrug resistance phenotype in human hepatocellular carcinoma cells cannot be attributed to expression of the MDR1 gene, but that novel mechanisms may account for the resistance of these cancer cells.

P-glycoprotein as the drug efflux pump in primary cultured bovine brain capillary endothelial cells

Life Sciences ◽  
1992 ◽  
Vol 51 (18) ◽  
pp. 1427-1437 ◽  
Author(s):  
Akira Tsuji ◽  
Tetsuya Terasaki ◽  
Yasushi Takabatake ◽  
Yoshiyuki Tenda ◽  
Ikumi Tamai ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Efflux Pump ◽  
Bovine Brain ◽  
Drug Efflux ◽  
Brain Capillary ◽  
Brain Capillary Endothelial Cells ◽  
P Glycoprotein ◽  
Capillary Endothelial Cells ◽  
Drug Efflux Pump

Modeling of P-glycoprotein-involved epithelial drug transport in MDCK cells

1999 ◽  
Vol 277 (1) ◽  
pp. F84-F96 ◽  
Author(s):  
Shinya Ito ◽  
Cindy Woodland ◽  
Balázs Sarkadi ◽  
Guido Hockmann ◽  
Scott E. Walker ◽  
...  
Keyword(s):  
Drug Transport ◽  
Diffusion Processes ◽  
Efflux Pump ◽  
Mdck Cells ◽  
Basolateral Membrane ◽  
Drug Efflux ◽  
Drug Transfer ◽  
P Glycoprotein ◽  
Drug Efflux Pump ◽  
Apical Membranes

P-glycoprotein (P-gp) on the apical membranes of epithelial cells is known as a drug efflux pump. However, unclear is its integral quantitative role in the overall epithelial drug transfer, which also involves distinct diffusion processes in parallel and sequence. We used a simple three-compartment model to obtain kinetic parameters of each drug transfer mechanism, which can quantitatively describe the transport time courses of P-gp substrates, digoxin and vinblastine, across P-gp-expressing MDCK cell monolayers grown on permeable filters. Our results show that the model, which assumes a functionally single drug efflux pump in the apical membrane with diffusion across two membranes and intercellular junctions, is the least complex model with which to quantitatively reproduce the characteristics of the data. Interestingly, the model predicts that the MDCK apical membranes are less diffusion permeable than the basolateral membrane for both drugs and that the distribution volume of vinblastine is 10-fold higher than that of digoxin. Additional experiments verified these model predictions. The modeling approach is feasible to quantitatively describe overall kinetic picture of epithelial drug transport. Further model refinement is necessary to incorporate other modes of drug transport such as transcytosis. Also, whether P-gp solely accounts for the pump function in this model awaits more studies.

Saturable Function of P-Glycoprotein as a Drug-efflux Pump in Multidrug-resistant Tumour Cells

1996 ◽  
Vol 48 (5) ◽  
pp. 522-525 ◽  
Author(s):  
KEN-ICHI MIYAMOTO ◽  
KEIKO KOGA-TAKEDA ◽  
KENJIRO KOGA ◽  
TAEYUKI OHSHIMA ◽  
MASAAKI NOMURA
Keyword(s):  
Efflux Pump ◽  
Multidrug Resistant ◽  
Tumour Cells ◽  
Drug Efflux ◽  
P Glycoprotein ◽  
Drug Efflux Pump

scholarly journals RamA Is an Alternate Activator of the Multidrug Resistance Cascade in Enterobacter aerogenes

2004 ◽  
Vol 48 (7) ◽  
pp. 2518-2523 ◽  
Author(s):  
Renaud Chollet ◽  
Jacqueline Chevalier ◽  
Claude Bollet ◽  
Jean-Marie Pages ◽  
Anne Davin-Regli
Keyword(s):  
Escherichia Coli ◽  
Multidrug Resistance ◽  
Type Strain ◽  
Efflux Pump ◽  
Regulatory Protein ◽  
Enterobacter Aerogenes ◽  
Transcriptional Activator ◽  
Drug Efflux ◽  
Gene Encoding ◽  
Drug Efflux Pump

ABSTRACT Multidrug resistance (MDR) in Enterobacter aerogenes can be mediated by induction of MarA, which is triggered by certain antibiotics and phenolic compounds. In this study, we identified the gene encoding RamA, a 113-amino-acid regulatory protein belonging to the AraC-XylS transcriptional activator family, in the Enterobacter aerogenes ATCC 13048 type strain and in a clinical multiresistant isolate. Overexpression of RamA induced an MDR phenotype in drug-susceptible Escherichia coli JM109 and E. aerogenes ATCC 13048, as demonstrated by 2- to 16-fold-increased resistance to β-lactams, tetracycline, chloramphenicol, and quinolones, a decrease in porin production, and increased production of AcrA, a component of the AcrAB-TolC drug efflux pump. We show that RamA enhances the transcription of the marRAB operon but is also able to induce an MDR phenotype in a mar-deleted strain. We demonstrate here that RamA is a transcriptional activator of the Mar regulon and is also a self-governing activator of the MDR cascade.

scholarly journals The human multidrug resistance-associated protein MRP is a plasma membrane drug-efflux pump.

1994 ◽  
Vol 91 (19) ◽  
pp. 8822-8826 ◽  
Author(s):  
G. J. Zaman ◽  
M. J. Flens ◽  
M. R. van Leusden ◽  
M. de Haas ◽  
H. S. Mulder ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Multidrug Resistance ◽  
Efflux Pump ◽  
Drug Efflux ◽  
Drug Efflux Pump

scholarly journals Caffeic Acid Attenuates Multi-Drug Resistance in Cancer Cells by Inhibiting Efflux Function of Human P-Glycoprotein

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 247
Author(s):  
Yu-Ning Teng ◽  
Charles C.N. Wang ◽  
Wei-Chieh Liao ◽  
Yu-Hsuan Lan ◽  
Chin-Chuan Hung
Keyword(s):  
Atpase Activity ◽  
Caffeic Acid ◽  
Efflux Pump ◽  
Multi Drug Resistance ◽  
Drug Efflux ◽  
Promising Candidate ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Calcein Am ◽  
Drug Efflux Pump

Multidrug resistance (MDR) is a complicated ever-changing problem in cancer treatment, and P-glycoprotein (P-gp), a drug efflux pump, is regarded as the major cause. In the way of developing P-gp inhibitors, natural products such as phenolic acids have gotten a lot of attention recently. The aim of the present study was to investigate the modulating effects and mechanisms of caffeic acid on human P-gp, as well as the attenuating ability on cancer MDR. Calcein-AM, rhodamine123, and doxorubicin were used to analyze the interaction between caffeic acid and P-gp, and the ATPase activity of P-gp was evaluated as well. Resistance reversing effects were revealed by SRB and cell cycle assay. The results indicated that caffeic acid uncompetitively inhibited rhodamine123 efflux and competitively inhibited doxorubicin efflux. In terms of P-gp ATPase activity, caffeic acid exhibited stimulation in both basal and verapamil-stimulated activity. The combination of chemo drugs and caffeic acid resulted in decreased IC50 in ABCB1/Flp-InTM-293 and KB/VIN, indicating that the resistance was reversed. Results of molecular docking suggested that caffeic acid bound to P-gp through GLU74 and TRY117 residues. The present study demonstrated that caffeic acid is a promising candidate for P-gp inhibition and cancer MDR attenuation.

scholarly journals Berberine reverses multidrug resistance in Candida albicans by hijacking the drug efflux pump Mdr1p

2020 ◽  
Author(s):  
Yaojun Tong ◽  
Jingyu Zhang ◽  
Nuo Sun ◽  
Xiang-Ming Wang ◽  
Qi Wei ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Multidrug Resistance ◽  
Efflux Pump ◽  
Drug Efflux ◽  
Drug Efflux Pump

Membrane homoeostasis and multidrug resistance in yeast

2008 ◽  
Vol 28 (4) ◽  
pp. 217-228 ◽  
Author(s):  
Sneh Lata Panwar ◽  
Ritu Pasrija ◽  
Rajendra Prasad
Keyword(s):  
Multidrug Resistance ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Membrane Lipid ◽  
Major Facilitator Superfamily ◽  
Drug Efflux ◽  
Proper Functioning ◽  
Drug Efflux Pumps ◽  
Drug Efflux Pump ◽  
Major Facilitator

The development of MDR (multidrug resistance) in yeast is due to a number of mechanisms. The most documented mechanism is enhanced extrusion of drugs mediated by efflux pump proteins belonging to either the ABC (ATP-binding cassette) superfamily or MFS (major facilitator superfamily). These drug-efflux pump proteins are localized on the plasma membrane, and the milieu therein affects their proper functioning. Several recent studies demonstrate that fluctuations in membrane lipid composition affect the localization and proper functioning of the MDR efflux pump proteins. Interestingly, the efflux pumps of the ABC superfamily are particularly susceptible to imbalances in membrane-raft lipid constituents. This review focuses on the importance of the membrane environment in functioning of the drug-efflux pumps and explores a correlation between MDR and membrane lipid homoeostasis.

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