Reversal of P-glycoprotein-mediated multidrug resistance by ginsenoside Rg(3)
Multidrug resistance has been a major problem in cancer chemotherapy. In this study, in vitro and in vivo modulations of MDR by ginsenoside Rg(3), a red ginseng saponin, were investigated. In flow cytometric analysis using rhodamine 123 as an artificial substrate, Rg(3) promoted accumulation of rhod...
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| Veröffentlicht in: | Biochemical pharmacology 2003-01, Vol.65 (1), p.75-82 |
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| creator | Kim, Seung-Whan Kwon, Hyog-young Chi, Dong-Whan Shim, Jai-Heon Park, Jong-Dae Lee, You-Hui Pyo, Suhkneung Rhee, Dong-Kwon |
| description | Multidrug resistance has been a major problem in cancer chemotherapy. In this study, in vitro and in vivo modulations of MDR by ginsenoside Rg(3), a red ginseng saponin, were investigated. In flow cytometric analysis using rhodamine 123 as an artificial substrate, Rg(3) promoted accumulation of rhodamine 123 in drug-resistant KBV20C cells in a dose-dependent manner, but it had no effect on parental KB cells. Additionally Rg(3) inhibited [3H]vinblastine efflux and reversed MDR to doxorubicin, COL, VCR, and VP-16 in KBV20C cells. Reverse transcriptase-polymerase chain reaction and immuno-blot analysis after exposure of KBV20C cells to Rg(3) showed that inhibition of drug efflux by Rg(3) was due to neither repression of MDR1 gene expression nor Pgp level. Photo-affinity labeling study with [3H]azidopine, however, revealed that Rg(3) competed with [3H]azidopine for binding to the Pgp demonstrating that Rg(3) competed with anticancer drug for binding to Pgp thereby blocking drug efflux. Furthermore, Rg(3) increased life span in mice implanted with DOX-resistant murine leukemia P388 cells in vivo and inhibited body weight increase significantly. |
| doi_str_mv | 10.1016/S0006-2952(02)01446-6 |
| format | Article |
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In this study, in vitro and in vivo modulations of MDR by ginsenoside Rg(3), a red ginseng saponin, were investigated. In flow cytometric analysis using rhodamine 123 as an artificial substrate, Rg(3) promoted accumulation of rhodamine 123 in drug-resistant KBV20C cells in a dose-dependent manner, but it had no effect on parental KB cells. Additionally Rg(3) inhibited [3H]vinblastine efflux and reversed MDR to doxorubicin, COL, VCR, and VP-16 in KBV20C cells. Reverse transcriptase-polymerase chain reaction and immuno-blot analysis after exposure of KBV20C cells to Rg(3) showed that inhibition of drug efflux by Rg(3) was due to neither repression of MDR1 gene expression nor Pgp level. Photo-affinity labeling study with [3H]azidopine, however, revealed that Rg(3) competed with [3H]azidopine for binding to the Pgp demonstrating that Rg(3) competed with anticancer drug for binding to Pgp thereby blocking drug efflux. Furthermore, Rg(3) increased life span in mice implanted with DOX-resistant murine leukemia P388 cells in vivo and inhibited body weight increase significantly.</description><identifier>ISSN: 0006-2952</identifier><identifier>DOI: 10.1016/S0006-2952(02)01446-6</identifier><identifier>PMID: 12473381</identifier><language>eng</language><publisher>England</publisher><subject>Affinity Labels - metabolism ; Animals ; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism ; ATP Binding Cassette Transporter, Subfamily B, Member 1 - physiology ; Azides - metabolism ; Biological Transport - drug effects ; Dihydropyridines - metabolism ; Disease Models, Animal ; Drug Resistance, Multiple - physiology ; Fluorescent Dyes - metabolism ; Ginsenosides - pharmacology ; Ginsenosides - therapeutic use ; Humans ; KB Cells ; Leukemia P388 - drug therapy ; Leukemia P388 - mortality ; Mice ; Rhodamine 123 - metabolism ; Tritium ; Tumor Cells, Cultured ; Vinblastine - pharmacokinetics</subject><ispartof>Biochemical pharmacology, 2003-01, Vol.65 (1), p.75-82</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c191t-56342cf143b990b0e1c35065a9a582033f096e00c45e53a6bb380e87f3625aa53</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12473381$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Seung-Whan</creatorcontrib><creatorcontrib>Kwon, Hyog-young</creatorcontrib><creatorcontrib>Chi, Dong-Whan</creatorcontrib><creatorcontrib>Shim, Jai-Heon</creatorcontrib><creatorcontrib>Park, Jong-Dae</creatorcontrib><creatorcontrib>Lee, You-Hui</creatorcontrib><creatorcontrib>Pyo, Suhkneung</creatorcontrib><creatorcontrib>Rhee, Dong-Kwon</creatorcontrib><title>Reversal of P-glycoprotein-mediated multidrug resistance by ginsenoside Rg(3)</title><title>Biochemical pharmacology</title><addtitle>Biochem Pharmacol</addtitle><description>Multidrug resistance has been a major problem in cancer chemotherapy. In this study, in vitro and in vivo modulations of MDR by ginsenoside Rg(3), a red ginseng saponin, were investigated. In flow cytometric analysis using rhodamine 123 as an artificial substrate, Rg(3) promoted accumulation of rhodamine 123 in drug-resistant KBV20C cells in a dose-dependent manner, but it had no effect on parental KB cells. Additionally Rg(3) inhibited [3H]vinblastine efflux and reversed MDR to doxorubicin, COL, VCR, and VP-16 in KBV20C cells. Reverse transcriptase-polymerase chain reaction and immuno-blot analysis after exposure of KBV20C cells to Rg(3) showed that inhibition of drug efflux by Rg(3) was due to neither repression of MDR1 gene expression nor Pgp level. Photo-affinity labeling study with [3H]azidopine, however, revealed that Rg(3) competed with [3H]azidopine for binding to the Pgp demonstrating that Rg(3) competed with anticancer drug for binding to Pgp thereby blocking drug efflux. Furthermore, Rg(3) increased life span in mice implanted with DOX-resistant murine leukemia P388 cells in vivo and inhibited body weight increase significantly.</description><subject>Affinity Labels - metabolism</subject><subject>Animals</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 1 - physiology</subject><subject>Azides - metabolism</subject><subject>Biological Transport - drug effects</subject><subject>Dihydropyridines - metabolism</subject><subject>Disease Models, Animal</subject><subject>Drug Resistance, Multiple - physiology</subject><subject>Fluorescent Dyes - metabolism</subject><subject>Ginsenosides - pharmacology</subject><subject>Ginsenosides - therapeutic use</subject><subject>Humans</subject><subject>KB Cells</subject><subject>Leukemia P388 - drug therapy</subject><subject>Leukemia P388 - mortality</subject><subject>Mice</subject><subject>Rhodamine 123 - metabolism</subject><subject>Tritium</subject><subject>Tumor Cells, Cultured</subject><subject>Vinblastine - pharmacokinetics</subject><issn>0006-2952</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9UE1PwzAUywHExuAngHpC2yHwktek6RFN40MaAg04V2n6WgX1YzQt0v49QwxOli3Lss3YhYBrAULfvAKA5jJVcg5yASKONddHbPovT9hpCB8_1GhxwiZCxgmiEVP2tKEv6oOto66MXnhV71y37buBfMsbKrwdqIiasR580Y9V1FPwYbCtoyjfRZVvA7Vd8AVFm2qOizN2XNo60PkBZ-z9bvW2fODr5_vH5e2aO5GKgSuNsXSliDFPU8iBhEMFWtnUKiMBsYRUE4CLFSm0Os_RAJmkRC2VtQpn7Oo3d1_1c6QwZI0PjurattSNIUukMRITszdeHoxjvp-TbXvf2H6X_R2A3yPVWwA</recordid><startdate>20030101</startdate><enddate>20030101</enddate><creator>Kim, Seung-Whan</creator><creator>Kwon, Hyog-young</creator><creator>Chi, Dong-Whan</creator><creator>Shim, Jai-Heon</creator><creator>Park, Jong-Dae</creator><creator>Lee, You-Hui</creator><creator>Pyo, Suhkneung</creator><creator>Rhee, Dong-Kwon</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20030101</creationdate><title>Reversal of P-glycoprotein-mediated multidrug resistance by ginsenoside Rg(3)</title><author>Kim, Seung-Whan ; Kwon, Hyog-young ; Chi, Dong-Whan ; Shim, Jai-Heon ; Park, Jong-Dae ; Lee, You-Hui ; Pyo, Suhkneung ; Rhee, Dong-Kwon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c191t-56342cf143b990b0e1c35065a9a582033f096e00c45e53a6bb380e87f3625aa53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Affinity Labels - metabolism</topic><topic>Animals</topic><topic>ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism</topic><topic>ATP Binding Cassette Transporter, Subfamily B, Member 1 - physiology</topic><topic>Azides - metabolism</topic><topic>Biological Transport - drug effects</topic><topic>Dihydropyridines - metabolism</topic><topic>Disease Models, Animal</topic><topic>Drug Resistance, Multiple - physiology</topic><topic>Fluorescent Dyes - metabolism</topic><topic>Ginsenosides - pharmacology</topic><topic>Ginsenosides - therapeutic use</topic><topic>Humans</topic><topic>KB Cells</topic><topic>Leukemia P388 - drug therapy</topic><topic>Leukemia P388 - mortality</topic><topic>Mice</topic><topic>Rhodamine 123 - metabolism</topic><topic>Tritium</topic><topic>Tumor Cells, Cultured</topic><topic>Vinblastine - pharmacokinetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Seung-Whan</creatorcontrib><creatorcontrib>Kwon, Hyog-young</creatorcontrib><creatorcontrib>Chi, Dong-Whan</creatorcontrib><creatorcontrib>Shim, Jai-Heon</creatorcontrib><creatorcontrib>Park, Jong-Dae</creatorcontrib><creatorcontrib>Lee, You-Hui</creatorcontrib><creatorcontrib>Pyo, Suhkneung</creatorcontrib><creatorcontrib>Rhee, Dong-Kwon</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Seung-Whan</au><au>Kwon, Hyog-young</au><au>Chi, Dong-Whan</au><au>Shim, Jai-Heon</au><au>Park, Jong-Dae</au><au>Lee, You-Hui</au><au>Pyo, Suhkneung</au><au>Rhee, Dong-Kwon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reversal of P-glycoprotein-mediated multidrug resistance by ginsenoside Rg(3)</atitle><jtitle>Biochemical pharmacology</jtitle><addtitle>Biochem Pharmacol</addtitle><date>2003-01-01</date><risdate>2003</risdate><volume>65</volume><issue>1</issue><spage>75</spage><epage>82</epage><pages>75-82</pages><issn>0006-2952</issn><abstract>Multidrug resistance has been a major problem in cancer chemotherapy. In this study, in vitro and in vivo modulations of MDR by ginsenoside Rg(3), a red ginseng saponin, were investigated. In flow cytometric analysis using rhodamine 123 as an artificial substrate, Rg(3) promoted accumulation of rhodamine 123 in drug-resistant KBV20C cells in a dose-dependent manner, but it had no effect on parental KB cells. Additionally Rg(3) inhibited [3H]vinblastine efflux and reversed MDR to doxorubicin, COL, VCR, and VP-16 in KBV20C cells. Reverse transcriptase-polymerase chain reaction and immuno-blot analysis after exposure of KBV20C cells to Rg(3) showed that inhibition of drug efflux by Rg(3) was due to neither repression of MDR1 gene expression nor Pgp level. Photo-affinity labeling study with [3H]azidopine, however, revealed that Rg(3) competed with [3H]azidopine for binding to the Pgp demonstrating that Rg(3) competed with anticancer drug for binding to Pgp thereby blocking drug efflux. Furthermore, Rg(3) increased life span in mice implanted with DOX-resistant murine leukemia P388 cells in vivo and inhibited body weight increase significantly.</abstract><cop>England</cop><pmid>12473381</pmid><doi>10.1016/S0006-2952(02)01446-6</doi><tpages>8</tpages></addata></record> |
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| subjects | Affinity Labels - metabolism Animals ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism ATP Binding Cassette Transporter, Subfamily B, Member 1 - physiology Azides - metabolism Biological Transport - drug effects Dihydropyridines - metabolism Disease Models, Animal Drug Resistance, Multiple - physiology Fluorescent Dyes - metabolism Ginsenosides - pharmacology Ginsenosides - therapeutic use Humans KB Cells Leukemia P388 - drug therapy Leukemia P388 - mortality Mice Rhodamine 123 - metabolism Tritium Tumor Cells, Cultured Vinblastine - pharmacokinetics |
| title | Reversal of P-glycoprotein-mediated multidrug resistance by ginsenoside Rg(3) |
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