scholarly journals Modulation of Multidrug Resistance by Artemisinin, Artesunate and Dihydroartemisinin in K562/adr and GLC4/adr Resistant Cell Lines

2002 ◽  
Vol 25 (12) ◽  
pp. 1555-1561 ◽  
Author(s):  
Paiboon Reungpatthanaphong ◽  
Samlee Mankhetkorn
Keyword(s):  
Multidrug Resistance ◽  
Cell Lines ◽  
Resistant Cell

Imatinib Is a Substrate for Various Multidrug Resistance Proteins

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4249-4249
Author(s):  
Krzysztof Czyzewski ◽  
Jan Styczynski
Keyword(s):  
Multidrug Resistance ◽  
Chronic Myeloid Leukemia ◽  
Cell Line ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Resistant Cell ◽  
Multidrug Resistance Proteins ◽  
Resistance Proteins ◽  
Imatinib Resistant ◽  
Ic50 Value

Abstract An increasing resistance to imatinib is an emerging problem in patients with chronic myeloid leukemia. The aim of the study was assessing possible mechanisms of cellular drug resistance in imatinib-resistant derivates of chronic myeloid leukemia K-562 cell line. A parental K-562 and its imatinib-resistant derivate cell lines were used. Cell lines were tested for cytotoxicity of imatinib, cytarabine, busulfan and etoposide. Multidrug resistance proteins expression, rhodamine retention and daunorubicin accumulation were measured for each cell line. Imatinib was cytotoxic to all tested groups of cells. Exposition of K-562 cell line to low concentrations of imatinib caused an increase of IC50 value of imatinib, while exposition of K-562 cell line to higher concentrations of imatinib decreased IC50 value of imatinib. There was a high correlation between PGP, MRP1 and LRP expression and IC50 for imatinib and etoposide. All tested cell lines were highly resistant to cytarabine. Rhodamine retention alone and in the presence of cyclosporine was the lowest in imatinib-resistant K-562R-0.1 cell line, what suggest high PGP activity in this cell line. Daunorubicin accumulation was the highest in parental K-562 cell line and it decreased in imatinib-resistant cell lines, which were characterized by high PGP, MRP1 and LRP expression. These data suggest that imatinib is a substrate for multidrug resistance proteins, and an increased expression of PGP, MRP1 and LRP play a role in resistance to imatinib in chronic myeloid leukemia.

scholarly journals Enhancing the Therapeutic Efficacy of Daunorubicin and Mitoxantrone with Bavachinin, Candidone, and Tephrosin

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Sina Darzi ◽  
Seyed Abbas Mirzaei ◽  
Fatemeh Elahian ◽  
Sadegh Shirian ◽  
Amir Peymani ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cancer Treatment ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell Line ◽  
Multidrug Resistant ◽  
Resistant Cell ◽  
Dependent Manner ◽  
Expression Levels ◽  
Treatment Research

The capability of flavonoids in sensitizing cancer cells was demonstrated in numerous works to chemotherapy and converse multidrug resistance by modulating efflux pumps and apoptosis mechanisms. Three flavonoids, namely, bavachinin, tephrosin, and candidone, have been recently introduced to cancer treatment research presenting various activities, such as antibacterial, immunomodulatory, cell death, and anticancer. Less information exists regarding the therapeutic significance of these flavonoids in cancer treatment, especially in overcoming multidrug resistance (MDR). Here, we tempted to investigate the potency of these agents in reversing MDR by analyzing their effects as chemosensitizers on cell cytotoxicity, P-gp and ABCG2 protein expression levels, and their function on two multidrug-resistant cell lines, P-gp-overexpressing human gastric adenocarcinoma cell line (EPG85.257RDB) and ABCG2-overexpressing human epithelial breast cancer cell line (MCF7/MX). The inhibitory concentration of 10% (IC10) of bavachinin, tephrosin, and candidone in EPG85.257RDB cells was 1588.7 ± 202.2, 264.8 ± 86.15, and 1338.6 ± 114.11 nM, respectively. Moreover, these values in MCF7/MX cell were 2406.4 ± 257.63, 38.8 ± 4.28, and 27.9 ± 5.59 nM, respectively. Expression levels of ABCG2 and P-gp were not significantly downregulated by these flavonoids. Maximum levels of daunorubicin and mitoxantrone accumulations and minimum rates of drug efflux in both cell lines were detected 48 hrs posttreatment with tephrosin and bavachinin, respectively. Chemosensitization to mitoxantrone and daunorubicin treatments was, respectively, achieved in MCF7/MX and EPG85.257RDB cells in response to IC10 of bavachinin and tephrosin, independently. These effects did not follow time-dependent manner, and each flavonoid had its cell-dependent patterns. Overall, bavachinin, tephrosin, and candidone showed potency to sensitize MDR cells to daunorubicin and mitoxantrone and could be considered as attractive MDR modulators for cancer treatment. However, their action was time and cell specific.

scholarly journals Expression of the multidrug resistance associated protein and P- glycoprotein in doxorubicin-selected human myeloid leukemia cells

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3113-3121 ◽  
Author(s):  
CA Slapak ◽  
N Mizunuma ◽  
DW Kufe
Keyword(s):  
Multidrug Resistance ◽  
Cell Lines ◽  
Blot Analysis ◽  
Myeloid Leukemia ◽  
Resistant Cell ◽  
Drug Accumulation ◽  
Drug Resistant ◽  
Mdr1 Expression ◽  
Drug Resistant Cell ◽  
Vesicular Compartment

Abstract Drug-resistant sublines of the human U-937 myeloid leukemia cell line were selected in doxorubicin concentrations of 10, 40, and 200 ng/mL (designated U-A10, U-A40, and U-A200, respectively). Northern blot analysis showed overexpression of the multidrug resistance-associated protein (MRP) gene, but not MDR1, in U-A10 cells as compared with parental U-937 cells. Prolonged passage of U-A10 cells in 10 ng/mL of doxorubicin had little effect on MRP RNA levels, but increased MDR1 expression. The U-A40 and U-A200 cells, derived by selection of U-A10 cells, showed high levels of both MRP and MDR1 expression. None of the drug-resistant cell lines showed MRP or MDR1 gene amplification as judged by Southern blot analysis. U-A10 cells exhibited minimal decreased net accumulation of anthracycline, whereas U-A40 and U-A200 cells showed more significantly decreased drug accumulation as compared with U-937 cells. Subcellular anthracycline accumulation in U-937 cells as determined by fluorescence microscopy showed daunorubicin fluorescence predominately in the nucleus. However, the drug-resistant cell lines showed minimal nuclear drug accumulation with marked redistribution of drug into a vesicular compartment. Treatment with sodium azide/2-deoxyglucose, 2,4-dinitrophenol, or monensin, but not verapamil, abolished the vesicular accumulation. These studies in doxorubicin-selected U-937 cells indicate that induction of MRP overexpression occurs before that for the MDR1 gene. In addition, the drug-resistant cells possess an energy-dependent redistribution of anthracyclines into a nonnuclear vesicular compartment.

Cross-resistance to antifolates in multidrug resistant cell lines with P-glycoprotein or multidrug resistance protein expression

1997 ◽  
Vol 53 (12) ◽  
pp. 1855-1866 ◽  
Author(s):  
Baukelien van Triest ◽  
Herbert M. Pinedo ◽  
Frank Telleman ◽  
Clasina L. van der Wilt ◽  
Gerrit Jansen ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Protein Expression ◽  
Cell Lines ◽  
Multidrug Resistant ◽  
Resistant Cell ◽  
Cross Resistance ◽  
Multidrug Resistance Protein ◽  
P Glycoprotein ◽  
Resistance Protein

scholarly journals Expression of the multidrug resistance associated protein and P- glycoprotein in doxorubicin-selected human myeloid leukemia cells

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3113-3121 ◽  
Author(s):  
CA Slapak ◽  
N Mizunuma ◽  
DW Kufe
Keyword(s):  
Multidrug Resistance ◽  
Cell Lines ◽  
Blot Analysis ◽  
Myeloid Leukemia ◽  
Resistant Cell ◽  
Drug Accumulation ◽  
Drug Resistant ◽  
Mdr1 Expression ◽  
Drug Resistant Cell ◽  
Vesicular Compartment

Drug-resistant sublines of the human U-937 myeloid leukemia cell line were selected in doxorubicin concentrations of 10, 40, and 200 ng/mL (designated U-A10, U-A40, and U-A200, respectively). Northern blot analysis showed overexpression of the multidrug resistance-associated protein (MRP) gene, but not MDR1, in U-A10 cells as compared with parental U-937 cells. Prolonged passage of U-A10 cells in 10 ng/mL of doxorubicin had little effect on MRP RNA levels, but increased MDR1 expression. The U-A40 and U-A200 cells, derived by selection of U-A10 cells, showed high levels of both MRP and MDR1 expression. None of the drug-resistant cell lines showed MRP or MDR1 gene amplification as judged by Southern blot analysis. U-A10 cells exhibited minimal decreased net accumulation of anthracycline, whereas U-A40 and U-A200 cells showed more significantly decreased drug accumulation as compared with U-937 cells. Subcellular anthracycline accumulation in U-937 cells as determined by fluorescence microscopy showed daunorubicin fluorescence predominately in the nucleus. However, the drug-resistant cell lines showed minimal nuclear drug accumulation with marked redistribution of drug into a vesicular compartment. Treatment with sodium azide/2-deoxyglucose, 2,4-dinitrophenol, or monensin, but not verapamil, abolished the vesicular accumulation. These studies in doxorubicin-selected U-937 cells indicate that induction of MRP overexpression occurs before that for the MDR1 gene. In addition, the drug-resistant cells possess an energy-dependent redistribution of anthracyclines into a nonnuclear vesicular compartment.

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