Budesonide reduces multidrug resistance-associated protein 1 expression in an airway epithelial cell line (Calu-1)

The objective of this study was to determine the expression and activity of multidrug resistance-associated protein (MRP1) in a human airway epithelial cell line (Calu-1) and to further assess whether budesonide, a potent antiasthma corticosteroid, alters the expression and activity of MRP1 in these...

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Veröffentlicht in:European journal of pharmacology 2002-02, Vol.437 (1), p.9-17
Hauptverfasser: Bandi, Nagesh, Kompella, Uday B
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description The objective of this study was to determine the expression and activity of multidrug resistance-associated protein (MRP1) in a human airway epithelial cell line (Calu-1) and to further assess whether budesonide, a potent antiasthma corticosteroid, alters the expression and activity of MRP1 in these cells. Reverse transcriptase polymerase chain reaction (RT-PCR) and the Western blot analysis demonstrated the MRP1 mRNA and MRP1 protein in Calu-1 cells. Indomethacin, probenecid, and verapamil significantly enhanced the fluorescein accumulation and reduced the fluorescein efflux, consistent with the MRP1 activity in the Calu-1 cells. Following 14-day budesonide treatment, fluorescein accumulation increased and fluorescein efflux decreased, consistent with the inhibition of MRP1 activity by budesonide. At a concentration (10 μM) devoid of cytotoxicity, budesonide treatment decreased MRP1 mRNA and MRP1 protein expression in Calu-1 cells by 38% and 42%, respectively. In addition, budesonide (10 μM) enhanced the sensitivity of the MRP1 overexpressing COR-L23R cells to vincristine, suggesting the chemosensitizing effect of budesonide. Thus, budesonide inhibits MRP1 expression and may be useful as a chemosensitizer in tumor chemotherapy.
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Reverse transcriptase polymerase chain reaction (RT-PCR) and the Western blot analysis demonstrated the MRP1 mRNA and MRP1 protein in Calu-1 cells. Indomethacin, probenecid, and verapamil significantly enhanced the fluorescein accumulation and reduced the fluorescein efflux, consistent with the MRP1 activity in the Calu-1 cells. Following 14-day budesonide treatment, fluorescein accumulation increased and fluorescein efflux decreased, consistent with the inhibition of MRP1 activity by budesonide. At a concentration (10 μM) devoid of cytotoxicity, budesonide treatment decreased MRP1 mRNA and MRP1 protein expression in Calu-1 cells by 38% and 42%, respectively. In addition, budesonide (10 μM) enhanced the sensitivity of the MRP1 overexpressing COR-L23R cells to vincristine, suggesting the chemosensitizing effect of budesonide. 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Antiinflammatory agents ; Bronchodilator Agents - pharmacology ; Budesonide ; Budesonide - pharmacology ; Calu-1 cell ; Cell Line ; Cell Survival - drug effects ; Combined treatments (chemotherapy of immunotherapy associated with an other treatment) ; Dose-Response Relationship, Drug ; Epithelial Cells - drug effects ; Epithelial Cells - metabolism ; Gene Expression Regulation - drug effects ; Humans ; Indomethacin - pharmacology ; Lung - cytology ; Lung - drug effects ; Lung - metabolism ; Medical sciences ; MRP (Multidrug resistance-associated protein) ; Multidrug Resistance-Associated Proteins - drug effects ; Multidrug Resistance-Associated Proteins - genetics ; Multidrug Resistance-Associated Proteins - metabolism ; Pharmacology. 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Reverse transcriptase polymerase chain reaction (RT-PCR) and the Western blot analysis demonstrated the MRP1 mRNA and MRP1 protein in Calu-1 cells. Indomethacin, probenecid, and verapamil significantly enhanced the fluorescein accumulation and reduced the fluorescein efflux, consistent with the MRP1 activity in the Calu-1 cells. Following 14-day budesonide treatment, fluorescein accumulation increased and fluorescein efflux decreased, consistent with the inhibition of MRP1 activity by budesonide. At a concentration (10 μM) devoid of cytotoxicity, budesonide treatment decreased MRP1 mRNA and MRP1 protein expression in Calu-1 cells by 38% and 42%, respectively. In addition, budesonide (10 μM) enhanced the sensitivity of the MRP1 overexpressing COR-L23R cells to vincristine, suggesting the chemosensitizing effect of budesonide. Thus, budesonide inhibits MRP1 expression and may be useful as a chemosensitizer in tumor chemotherapy.</description><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Bones, joints and connective tissue. Antiinflammatory agents</subject><subject>Bronchodilator Agents - pharmacology</subject><subject>Budesonide</subject><subject>Budesonide - pharmacology</subject><subject>Calu-1 cell</subject><subject>Cell Line</subject><subject>Cell Survival - drug effects</subject><subject>Combined treatments (chemotherapy of immunotherapy associated with an other treatment)</subject><subject>Dose-Response Relationship, Drug</subject><subject>Epithelial Cells - drug effects</subject><subject>Epithelial Cells - metabolism</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Humans</subject><subject>Indomethacin - pharmacology</subject><subject>Lung - cytology</subject><subject>Lung - drug effects</subject><subject>Lung - metabolism</subject><subject>Medical sciences</subject><subject>MRP (Multidrug resistance-associated protein)</subject><subject>Multidrug Resistance-Associated Proteins - drug effects</subject><subject>Multidrug Resistance-Associated Proteins - genetics</subject><subject>Multidrug Resistance-Associated Proteins - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Probenecid - pharmacology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - drug effects</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Time Factors</subject><subject>Verapamil - pharmacology</subject><subject>Vincristine - pharmacology</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1v1DAQhq2Kii6Fn1DkC1V7CIwdx1mfqnYFFKkSB-BsOfYEjLzJ4kn68e_r7a7osdJIo7GeGb96GDsR8FGA0J9-AAhVSWPMGchzEFK3FRywhVi2poJWyFds8R85Ym-I_gJAY2Tzmh0JsdRK1_WC5as5II1DDMgzhtkj8fWcphjy_Lu8UKTJDR4rRzT66CYMfJPHCePABcf7TUEojgMvsysV85174LiJ0x9M0SXuMSWe4oD8bOXSXInzt-ywd4nw3b4fs19fPv9cXVc3379-W13eVF6peqqcl16IkliFUHdL2XRaOdF00vToNWDf-b5D7cFBcGA6o2vfCSNB-aD70NbH7HR3t-T9NyNNdh1pG8cNOM5kW6HaZQ1bsNmBPo9EGXu7yXHt8oMVYLey7ZNsuzVpQdon2RbK3vv9B3O3xvC8tbdbgA97wJF3qc_FZKRnrlZGN40p3MWOw6LjNmK25CMW6yFm9JMNY3whyiPFv516</recordid><startdate>20020215</startdate><enddate>20020215</enddate><creator>Bandi, Nagesh</creator><creator>Kompella, Uday B</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20020215</creationdate><title>Budesonide reduces multidrug resistance-associated protein 1 expression in an airway epithelial cell line (Calu-1)</title><author>Bandi, Nagesh ; Kompella, Uday B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-ac2c110594dd3b825b64a15b29fec60efbcfbe6c0a0da09b963cb19204cd6fd73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Bones, joints and connective tissue. Antiinflammatory agents</topic><topic>Bronchodilator Agents - pharmacology</topic><topic>Budesonide</topic><topic>Budesonide - pharmacology</topic><topic>Calu-1 cell</topic><topic>Cell Line</topic><topic>Cell Survival - drug effects</topic><topic>Combined treatments (chemotherapy of immunotherapy associated with an other treatment)</topic><topic>Dose-Response Relationship, Drug</topic><topic>Epithelial Cells - drug effects</topic><topic>Epithelial Cells - metabolism</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Humans</topic><topic>Indomethacin - pharmacology</topic><topic>Lung - cytology</topic><topic>Lung - drug effects</topic><topic>Lung - metabolism</topic><topic>Medical sciences</topic><topic>MRP (Multidrug resistance-associated protein)</topic><topic>Multidrug Resistance-Associated Proteins - drug effects</topic><topic>Multidrug Resistance-Associated Proteins - genetics</topic><topic>Multidrug Resistance-Associated Proteins - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Probenecid - pharmacology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - drug effects</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Time Factors</topic><topic>Verapamil - pharmacology</topic><topic>Vincristine - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bandi, Nagesh</creatorcontrib><creatorcontrib>Kompella, Uday B</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bandi, Nagesh</au><au>Kompella, Uday B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Budesonide reduces multidrug resistance-associated protein 1 expression in an airway epithelial cell line (Calu-1)</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2002-02-15</date><risdate>2002</risdate><volume>437</volume><issue>1</issue><spage>9</spage><epage>17</epage><pages>9-17</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>The objective of this study was to determine the expression and activity of multidrug resistance-associated protein (MRP1) in a human airway epithelial cell line (Calu-1) and to further assess whether budesonide, a potent antiasthma corticosteroid, alters the expression and activity of MRP1 in these cells. Reverse transcriptase polymerase chain reaction (RT-PCR) and the Western blot analysis demonstrated the MRP1 mRNA and MRP1 protein in Calu-1 cells. Indomethacin, probenecid, and verapamil significantly enhanced the fluorescein accumulation and reduced the fluorescein efflux, consistent with the MRP1 activity in the Calu-1 cells. Following 14-day budesonide treatment, fluorescein accumulation increased and fluorescein efflux decreased, consistent with the inhibition of MRP1 activity by budesonide. At a concentration (10 μM) devoid of cytotoxicity, budesonide treatment decreased MRP1 mRNA and MRP1 protein expression in Calu-1 cells by 38% and 42%, respectively. In addition, budesonide (10 μM) enhanced the sensitivity of the MRP1 overexpressing COR-L23R cells to vincristine, suggesting the chemosensitizing effect of budesonide. Thus, budesonide inhibits MRP1 expression and may be useful as a chemosensitizer in tumor chemotherapy.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>11864633</pmid><doi>10.1016/S0014-2999(02)01267-0</doi><tpages>9</tpages></addata></record>
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subjects Antineoplastic agents
Biological and medical sciences
Blotting, Western
Bones, joints and connective tissue. Antiinflammatory agents
Bronchodilator Agents - pharmacology
Budesonide
Budesonide - pharmacology
Calu-1 cell
Cell Line
Cell Survival - drug effects
Combined treatments (chemotherapy of immunotherapy associated with an other treatment)
Dose-Response Relationship, Drug
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Gene Expression Regulation - drug effects
Humans
Indomethacin - pharmacology
Lung - cytology
Lung - drug effects
Lung - metabolism
Medical sciences
MRP (Multidrug resistance-associated protein)
Multidrug Resistance-Associated Proteins - drug effects
Multidrug Resistance-Associated Proteins - genetics
Multidrug Resistance-Associated Proteins - metabolism
Pharmacology. Drug treatments
Probenecid - pharmacology
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - drug effects
RNA, Messenger - genetics
RNA, Messenger - metabolism
Time Factors
Verapamil - pharmacology
Vincristine - pharmacology
title Budesonide reduces multidrug resistance-associated protein 1 expression in an airway epithelial cell line (Calu-1)
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