CJZ3, a lomerizine derivative, reverses P-glycoprotein-mediated multidrug-resistance in doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells
P‐glycoprotein‐mediated drug efflux can yield a multidrug‐resistance (MDR) phenotype that is associated with a poor response to cancer chemotherapy. The development of safe and effective MDR‐reversing agents is an important approach in the clinic. The aim of this study was to examine the effects of...
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Veröffentlicht in: | Drug development research 2006-11, Vol.67 (11), p.862-869 |
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description | P‐glycoprotein‐mediated drug efflux can yield a multidrug‐resistance (MDR) phenotype that is associated with a poor response to cancer chemotherapy. The development of safe and effective MDR‐reversing agents is an important approach in the clinic. The aim of this study was to examine the effects of CJZ3, a lomerizine derivative, on the inhibition of P‐gp function and P‐gp‐mediated MDR in K562/DOX cells and parental K562 cells. Incubation of K562/DOX cells with CJZ3 caused a marked increase in accumulation and uptake and a notable decrease in efflux of Rh123, No such results were found in parental K562 cells. The inhibitory effect of the agent on P‐gp function was reversible, but it persisted for at least 90 min after removal of 2.5 &µM CJZ3 from the incubation medium. The doxorubicin‐induced cytotoxicity, apoptosis, and cell‐cycle perturbations were significantly potentiated by CJZ3. The intracellular accumulation of doxorubicin was enhanced in the presence of various concentrations of CJZ3. The CJZ3 exhibited potent effects in vitro in the reversal of P‐gp‐mediated MDR, suggesting that the compound may be an effective MDR reversing agent in cancer chemotherapy. Drug Dev. Res. 67:862–869, 2006. © 2007 Wiley‐Liss, Inc. |
doi_str_mv | 10.1002/ddr.20154 |
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The development of safe and effective MDR‐reversing agents is an important approach in the clinic. The aim of this study was to examine the effects of CJZ3, a lomerizine derivative, on the inhibition of P‐gp function and P‐gp‐mediated MDR in K562/DOX cells and parental K562 cells. Incubation of K562/DOX cells with CJZ3 caused a marked increase in accumulation and uptake and a notable decrease in efflux of Rh123, No such results were found in parental K562 cells. The inhibitory effect of the agent on P‐gp function was reversible, but it persisted for at least 90 min after removal of 2.5 &µM CJZ3 from the incubation medium. The doxorubicin‐induced cytotoxicity, apoptosis, and cell‐cycle perturbations were significantly potentiated by CJZ3. The intracellular accumulation of doxorubicin was enhanced in the presence of various concentrations of CJZ3. The CJZ3 exhibited potent effects in vitro in the reversal of P‐gp‐mediated MDR, suggesting that the compound may be an effective MDR reversing agent in cancer chemotherapy. Drug Dev. Res. 67:862–869, 2006. © 2007 Wiley‐Liss, Inc.</description><identifier>ISSN: 0272-4391</identifier><identifier>EISSN: 1098-2299</identifier><identifier>DOI: 10.1002/ddr.20154</identifier><identifier>CODEN: DDREDK</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Biological and medical sciences ; CJZ3 ; doxorubicin ; Medical sciences ; multidrug resistance ; P-glycoprotein ; Pharmacology. 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Res</addtitle><description>P‐glycoprotein‐mediated drug efflux can yield a multidrug‐resistance (MDR) phenotype that is associated with a poor response to cancer chemotherapy. The development of safe and effective MDR‐reversing agents is an important approach in the clinic. The aim of this study was to examine the effects of CJZ3, a lomerizine derivative, on the inhibition of P‐gp function and P‐gp‐mediated MDR in K562/DOX cells and parental K562 cells. Incubation of K562/DOX cells with CJZ3 caused a marked increase in accumulation and uptake and a notable decrease in efflux of Rh123, No such results were found in parental K562 cells. The inhibitory effect of the agent on P‐gp function was reversible, but it persisted for at least 90 min after removal of 2.5 &µM CJZ3 from the incubation medium. The doxorubicin‐induced cytotoxicity, apoptosis, and cell‐cycle perturbations were significantly potentiated by CJZ3. The intracellular accumulation of doxorubicin was enhanced in the presence of various concentrations of CJZ3. The CJZ3 exhibited potent effects in vitro in the reversal of P‐gp‐mediated MDR, suggesting that the compound may be an effective MDR reversing agent in cancer chemotherapy. Drug Dev. Res. 67:862–869, 2006. © 2007 Wiley‐Liss, Inc.</description><subject>Biological and medical sciences</subject><subject>CJZ3</subject><subject>doxorubicin</subject><subject>Medical sciences</subject><subject>multidrug resistance</subject><subject>P-glycoprotein</subject><subject>Pharmacology. 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Drug treatments</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ji, Bian-Sheng</creatorcontrib><creatorcontrib>He, Ling</creatorcontrib><creatorcontrib>Liu, Guo-Qing</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>CrossRef</collection><jtitle>Drug development research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ji, Bian-Sheng</au><au>He, Ling</au><au>Liu, Guo-Qing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CJZ3, a lomerizine derivative, reverses P-glycoprotein-mediated multidrug-resistance in doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells</atitle><jtitle>Drug development research</jtitle><addtitle>Drug Dev. 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The inhibitory effect of the agent on P‐gp function was reversible, but it persisted for at least 90 min after removal of 2.5 &µM CJZ3 from the incubation medium. The doxorubicin‐induced cytotoxicity, apoptosis, and cell‐cycle perturbations were significantly potentiated by CJZ3. The intracellular accumulation of doxorubicin was enhanced in the presence of various concentrations of CJZ3. The CJZ3 exhibited potent effects in vitro in the reversal of P‐gp‐mediated MDR, suggesting that the compound may be an effective MDR reversing agent in cancer chemotherapy. Drug Dev. Res. 67:862–869, 2006. © 2007 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><doi>10.1002/ddr.20154</doi><tpages>8</tpages></addata></record> |
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subjects | Biological and medical sciences CJZ3 doxorubicin Medical sciences multidrug resistance P-glycoprotein Pharmacology. Drug treatments |
title | CJZ3, a lomerizine derivative, reverses P-glycoprotein-mediated multidrug-resistance in doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells |
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