Interaction of tomato lectin with ABC transporter in cancer cells: Glycosylation confers functional conformation of P-gp

Date

2009-01-01

Author

Molnar, Joseph
Kars, Meltem Demirel
Gündüz, Ufuk
Engi, Helga
Schumacher, Udo
Van Damme, Els J.
Peumans, Willy J.
Makovitzky, Josef
Gyemant, Nora
Molnar, Peter

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

190
views

0
downloads

Phospho-glycoprotein (P-gP) is a polytopic plasma membrane protein whose overexpression causes multidrug resistance (MDR) responsible for the failure of cancer chemotherapy. P-gp 170 is a member of the ATP-binding cassette (ABC) transporter superfamily and has two potentially interesting regions for drugs interfering with its efflux function, namely the oligosaccharides on the first extracellular loop with unknown function and the two intracellular ATP-binding regions providing the energy for drug efflux function. The polylactoseamine oligosaccharides on the first loop can specifically bind the tomato lectin (TL). The P-gp efflux activities of TL-pre-treated MDR resistant cells were measured in the presence of structurally unrelated resistance modifiers such as phenothiazines, terpenoids and carotenoids. The inhibition of efflux activity was measured via the increased rhodamine uptake by mouse lymphoma cells transfected in human MDR1 gene and in human brain capillary endothelial cells. The tested resistance modifiers inhibit the function of ABC transporter resulting in increased 8123 accumulation in MDR1 expressing cells. TL prevented the inhibitory action of phenothiazine and verapamil on brain capillary endothelial and MDR1-lymphoma cells, presumably due to the stabilization of the functional active conformation of P-gp. Our results indicate that the polylactosamine chains of P-gp are part of the functionally active protein conformation. (C) 2008 Elsevier GmbH. All rights reserved.

Subject Keywords

Tomato lectin, Phospho-glycoprotein (P-gp), Multidrug resistance reversal, Glycosylation; MDR-1

URI

https://hdl.handle.net/11511/31932

Journal

ACTA HISTOCHEMICA

DOI

https://doi.org/10.1016/j.acthis.2008.11.010

Collections

Graduate School of Natural and Applied Sciences, Article

Suggestions

OpenMETU
Core

Effect of MDR modulators verapamil and promethazine on gene expression levels of MDR1 and MRP1 in doxorubicin-resistant MCF-7 cells Donmez, Yaprak; Akhmetova, Laila; Iseri, Ozlem Darcansoy; Kars, Meltem Demirel; Gündüz, Ufuk (2011-04-01) One of the major problems of cancer chemotherapy is the development of multidrug resistance (MDR) phenotype. Among the numerous mechanisms of MDR, a prominent one is the increased expression of membrane transporter proteins, the action of which leads to decreased intracellular drug concentration and cytotoxicity of drugs. Among them, P-gp and MRP1, encoded by MDR1 and MRP1 genes, respectively, have been associated with MDR phenotype. Chemical modulators can be used to reverse MDR. These chemicals can either...
Expression of Multidrug Resistance 1, Lung Resistance Protein and Breast Cancer Resistance Protein Genes in Chronic Leukemias Iseri, Ozlem D.; Kars, Meltem D.; Mutlu, Pelin; Avcu, Ferit; Ural, Ali U.; Gündüz, Ufuk (2011-01-01) One of the major problems in treatment of leukemias is multidrug resistance, which is already present at diagnosis or develops after chemotherapy. The gene expression levels of multidrug resistance resistance 1 (MDR1), breast cancer resistance protein (BCRP) and lung resistance-resistance protein (LRP) were evaluated in blood samples of 20 CLL and 24 CML patients using RT-PCR. MDR1, BCRP and LRP expression levels were detected in 65%, 20% and 45% of CLL patients, and in 54%, 37% and 25% of CML patients, res...
Effect of cobalt-60 (gamma radiation) on multidrug-resistant multiple myeloma cell lines Mutlu, Pelin; Ural, A. Ugur; Avcu, Ferit; Dirican, Bahar; Beyzadeoglu, Murat; Gündüz, Ufuk (2011-07-01) Emergence of resistance to chemotherapy and radiotherapy is a major obstacle for the successful treatment of MM (multiple myeloma). Prednisone, vincristine and melphalan are commonly used chemotherapeutic agents for the treatment of MM. In the current study, we examined the presence of possible cross-resistance between these drugs and gamma (gamma) radiation. Prednisone, vincristine and melphalan resistant RPMI-8226 and U-266 MM cells were generated by stepwise increasing concentrations of the drugs. The se...
Reversal of multidrug resistance by small interfering RNA (siRNA) in doxorubicin-resistant MCF-7 breast cancer cells Donmez, Yaprak; Gündüz, Ufuk (2011-03-01) Purpose: Resistance to anticancer drugs is a serious obstacle to cancer chemotherapy. A common form of multidrug resistance (MDR) is caused by the overexpression of transmembrane transporter proteins P-glycoprotein (P-gp) and multidrug resistance-associated protein-1 (MRP1), encoded by MDR1 and MRP1 genes, respectively. These proteins lead to reduced intracellular drug concentration and decreased cytotoxicity by means of their ability to pump the drugs out of the cells. Breast cancer tumor resistance is mai...
Identification of polymorphisms on the MDR1 gene among Turkish population and their effects on multidrug resistance in acute leukemia patients Kaya, P; Gündüz, Ufuk; Arpaci, F; Ural, AU; Guran, S (2005-09-01) Multidrug-resistance (MDR) phenotype is a serious limitation to the effective chemotherapeutic treatment of many cancer types, including leukemia. One of the most important proteins, the over-expression of which is responsible for the multidrug-resistance phenotype in many cancer types, is P-glycoprotein. This protein is the product of the MDR1 gene. In previous studies, single-nucleotide polymorphisms (SNPs) C3435T, G2677T, and T-129C in the MDR1 gene were shown to be correlated with lower P-glycoprotein e...

Citation Formats

J. Molnar et al., “Interaction of tomato lectin with ABC transporter in cancer cells: Glycosylation confers functional conformation of P-gp,” ACTA HISTOCHEMICA, pp. 330–334, 2009, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/31932.