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
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 modulate MDR due to their substrate analogy (such as calcium channel blocker verapamil) or interact with phospholipid membranes (such as antihistaminic drug promethazine). This study focuses on the effect of verapamil and promethazine on the expression levels of MDR1 and MRP1 genes and the drug transport activity in doxorubicin-resistant MCF-7 breast carcinoma cell line.


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...
Nanoparticles Based Drug Delivery Systems to Overcome Multidrug Resistance in Cancer The Role of Membrane Lipids Proteins and Carbohydrates
Özlüer, Özlem; Yalçın Azarkan, Serap; Gündüz, Ufuk (null; 2016-09-28)
Multidrug resistance (MDR) is a major problem in success of cancer chemotherapy on tumor cell growth, limits the prolonged and effective use of chemotherapy. The use of nanomaterial based drug carriers in cancer treatment offers exciting opportunities to enhance delivery of therapeutics to the tumor site (1). This is also known as targeted drug delivery providing differential distribution of drugs to the tumor site while significantly reducing the overall toxicity. Here, we critically discuss the role of th...
Interaction of tomato lectin with ABC transporter in cancer cells: Glycosylation confers functional conformation of P-gp
Molnar, Joseph; Kars, Meltem Demirel; Gündüz, Ufuk; Engi, Helga; Schumacher, Udo; Van Damme, Els J.; Peumans, Willy J.; Makovitzky, Josef; Gyemant, Nora; Molnar, Peter (2009-01-01)
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 fu...
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...
Citation Formats
Y. Donmez, L. Akhmetova, O. D. Iseri, M. D. Kars, and U. Gündüz, “Effect of MDR modulators verapamil and promethazine on gene expression levels of MDR1 and MRP1 in doxorubicin-resistant MCF-7 cells,” CANCER CHEMOTHERAPY AND PHARMACOLOGY, pp. 823–828, 2011, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/31348.