P-Glycoprotein-Mediated Efflux and Drug Sequestration in Lysosomes Confer Advantages of K562 Multidrug Resistance Sublines to Survive Prolonged Exposure to Cytotoxic Agents

Dechsupa, Nathupakorn; Mankhetkorn, Samlee

doi:10.3844/ajassp.2009.1637.1646

Cited by 6 publications

(6 citation statements)

References 21 publications

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“…Since we have previously demonstrated that the intracellular MDR transporters were also found localized on the intracellular organelle membrane and they also play important role on pumping the drugs from cytosol into these organelles for example in SiHa cells (Laochariyakul et al, 2003;Mankhetkorn and Garnier-Suillerot, 1998;Dechsupa and Mankhetkorn, 2009). In this study we preliminary determined that for K562/adr and GLC4/adr cells, the functional P-glycoprotein and MRP1 protein was localized on the plasma membrane (GarnierSuillerot et al, 2001).…”

Section: Discussionmentioning

confidence: 61%

Quercetin, Quercetrin Except Rutin Potentially Increased Pirarubicin Cytotoxicity by Non-Competitively Inhibiting the P-Glycoprotein-and MRP1 Function in Living K562/adr and GLC4/adr Cells

Choiprasert¹

2010

American Journal of Pharmacology and Toxicology

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Problem statement: Quercetin and its glycoside derivatives are increasingly receiving interests as new generation of anticancer molecules and were recognized by multidrug resistant transporters such as P-glycoprotein and MRP1 protein. Of relevance to their use as anticancer agents alone or in combination with other agents, this study aims to analyze the interaction of the compounds with the MDR transporters including P-glycoprotein and MRP1 protein in living multidrug resistant cells. Approach: The potential MDR reversing action of flavonoids was assessed by using the cotreatment of anticancer drug, pirarubicin or daunorubicin and quercetin, quercetrin or rutin compared with the series of co-treatment of pirarubicin or daunorubicin and the known inhibitor such as cyclosporine A and verapamil. The evidence of direct interaction of molecules with MDR protein was investigated by measuring the ability of inhibition of the rate of P-glycoprotein-and MRP1-mediated efflux of pirarubicin out of cells. Results: Quercetin and its glycoside derivatives efficiently inhibited cancer cell proliferation and re-sensitize the MDR cells to pirarubicin but not for daunorubicin. Our results clearly show that quercetin, quercetrin except rutin non-competitively inhibited the function of P-glycoprotein in K562/adr and MRP1 in GLC4/adr cells. The determined K I value of P-glycoprotein was equal to 0.33 µM for quercetin and 1 µM for quercetrin and K I value of MRP1 was equal to 0.45 µM for quercetin and 0.5 µM for quercetrin. Conclusion: The overall results demonstrated that quercetin, quercetrin and rutin should be considered as potential pharmaceutical molecules that might be used as MDR inhibitors.

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Section: Discussionmentioning

confidence: 61%

Quercetin, Quercetrin Except Rutin Potentially Increased Pirarubicin Cytotoxicity by Non-Competitively Inhibiting the P-Glycoprotein-and MRP1 Function in Living K562/adr and GLC4/adr Cells

Choiprasert¹

2010

American Journal of Pharmacology and Toxicology

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“…Previously, we indicated that low energy/low-doses of medical diagnostic X-rays did not significantly change various biological end points such as hemolysis, osmotic fragility, fluorescence anisotropy, mitochondrial membrane potential, the cell cycle, and the number of apoptotic cells of irradiated cells as compared to corresponding non-irradiated groups at each time end point [8][9][10] . Figure 2 summarizes the results as histograms of the accumulation of acridine orange in lysosomes.…”

Section: Resultsmentioning

confidence: 99%

Lysosomes of Cancerous and Normal cells in Response to Low-energy/low-dose Medical Diagnostic X-rays

Tungjai

Tubthaing

Kothan

2019

Bangladesh J Med Sci

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Background: Low-energy/low-dose ionizing radiation is increasingly being used in medical diagnosis, yet the effects of low-energy/low-dose medical diagnostic X-rays on biological systems remains a mystery. Thus, the aim of this present study is to determine the characteristics of lysosomes of cancerous and normal cells in response to low-energy/low-dose medical diagnostic X-rays. Methods and materials: Three cell lines composed of peripheral blood mononuclear cells (PBMCs), adriamycin-sensitive erythroleukemia cells (K562), and adriamycin-resistant erythroleukemia cells (K562/adr), were all exposed to low-energy/low-dose medical diagnostic X-rays that operated at 50, 70, and 100 kV, and 100 mAs for obtaining radiation doses at 0.03, 0.07, and 0.10 mGy, respectively. Accumulation of acridine orange in the lysosomes of each cell line was determined using flow cytometry completed at 4 and 6 hours-post irradiation. Results: The data showed an increase in fluorescence intensity of acridine orange in three irradiated cells line at 4 hours post-irradiation, but this intensity did not change at 6 hours post-irradiation when compared to that of corresponding non-irradiated cells. Conclusion: This finding suggests that changes in lysosomes might be a response to low-energy/low-dose medical diagnostic X-rays. Bangladesh Journal of Medical Science Vol.18(4) 2019 p.830-834

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“…Lysosomal function was studied by altering the accumulation of acridine orange (AO) in lysosomes. The staining method was modified from a previously published work 33,34 . Briefly, 10 6 cells were suspended in 2 mL PBS buffer, pH 7.25 at 37°C in the presence of 1µM AO for 5 minutes in the dark.…”

Section: Lysosomementioning

confidence: 99%

Effects of Medical Diagnostic X-rays Delivered at 0.01 or 0.05 mGy on Human Blood Cells

Supawat

Tinlapat

Wongmahamad

et al. 2021

Bangladesh J Med Sci

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Background: Low-dose X-rays are commonly used in medical imaging to help in the diagnosis ofdiseases. However, the deleterious effects of exposure to medical diagnostic low-dose X-rays remaina highly debated topic. The objective was to study the effects of medical diagnostic X-rays on humanblood cells. Materials and Methods: We studied the effects of medical diagnostic low-dose X-rays (80kVp), i.e.,0.01 or 0.05 mGy, after the in vitro exposure of human red blood cells (RBCs) and peripheralblood mononucleated cells (PBMCs).Cells with no irradiation served as the control group. The biologicalendpoints that were used to determine the effects of medical diagnostic low-dose X-rays were hemolysisfor RBCs and mitochondrial membrane potential, lysosomes, and the cell cycle for PBMCs. Results: Ourresults showed no changes in the hemolysis of RBCs and mitochondrial membrane potential, lysosome, orcell cycle in cells exposed to these low doses of X-rays when compared to the corresponding nonirradiatedcells at all harvest timepoints. Conclusion: These results suggested that there were no deleterious effectsof diagnostic low-dose X-rays when human RBCs and PBMCs were exposed in vitro. Bangladesh Journal of Medical Science Vol.20(1) 2021 p.136-144

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P-Glycoprotein-Mediated Efflux and Drug Sequestration in Lysosomes Confer Advantages of K562 Multidrug Resistance Sublines to Survive Prolonged Exposure to Cytotoxic Agents

Cited by 6 publications

References 21 publications

Quercetin, Quercetrin Except Rutin Potentially Increased Pirarubicin Cytotoxicity by Non-Competitively Inhibiting the P-Glycoprotein-and MRP1 Function in Living K562/adr and GLC4/adr Cells

Quercetin, Quercetrin Except Rutin Potentially Increased Pirarubicin Cytotoxicity by Non-Competitively Inhibiting the P-Glycoprotein-and MRP1 Function in Living K562/adr and GLC4/adr Cells

Lysosomes of Cancerous and Normal cells in Response to Low-energy/low-dose Medical Diagnostic X-rays

Effects of Medical Diagnostic X-rays Delivered at 0.01 or 0.05 mGy on Human Blood Cells

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