Synergism of energy starvation and dextran-conjugated doxorubicin in the killing of multidrug-resistant KB carcinoma cells
Here we report that 2-deoxyglucose/Na azide treatment and free/conjugated doxorubicin are synergistic in cell killing. As demonstrated by fluorescence confocal microscopy, KB-V1 cells retained more conjugated doxorubicin than free doxorubicin. Verapamil or 2-deoxyglucose/Na azide enhanced only the r...
Gespeichert in:
| Veröffentlicht in: | Anti-cancer drugs 1999-02, Vol.10 (2), p.171-178 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 178 |
|---|---|
| container_issue | 2 |
| container_start_page | 171 |
| container_title | Anti-cancer drugs |
| container_volume | 10 |
| creator | Lam, Wing Chan, Hingleung Yang, Mengsu Cheng, Shukhan Fong, Wangfun |
| description | Here we report that 2-deoxyglucose/Na azide treatment and free/conjugated doxorubicin are synergistic in cell killing. As demonstrated by fluorescence confocal microscopy, KB-V1 cells retained more conjugated doxorubicin than free doxorubicin. Verapamil or 2-deoxyglucose/Na azide enhanced only the retention of the free drug and the small ( |
| doi_str_mv | 10.1097/00001813-199902000-00005 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1097_00001813_199902000_00005</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>10211547</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3565-ed39bd74cbb1779e38b08fabca8028d59fbdc17924dece3c5e0a035fdc2827403</originalsourceid><addsrcrecordid>eNp1UctOwzAQtBAIyuMXkH_AYMcxjo-AeAkkDsA5cuxN69ZJkO1Ay9fjUkBcWK20u6OZOcwihBk9YVTJU5qLVYwTppSiRb7IGhJbaMJKyYmQJdtGE6qEIqWSfA_txzjPjIzzXbTHaMGYKOUEfTyteghTFzs8tBjW-wrHpMObTm7ose4ttrBMQffEDP18nOoEGRqWQxgbZ1yPc6cZ4IXz3vXTtU03-uRsGKckQHTZrU_4_gIbHTJ_6DQ24H08RDut9hGOvucBerm-er68JQ-PN3eX5w_EcHEmCFiuGitL0zRMSgW8amjV6sboihaVFaptrGFSFaUFA9wIoJpy0VpTVIUsKT9A1cbXhCHGAG39Glynw6pmtF7HWf_EWf_G-QWJLD3eSF_HpgP7R7jJLxPKDeF98AlCXPjxHUI9A-3TrP7vTfwTQvKDRg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Synergism of energy starvation and dextran-conjugated doxorubicin in the killing of multidrug-resistant KB carcinoma cells</title><source>MEDLINE</source><source>Journals@Ovid Complete</source><creator>Lam, Wing ; Chan, Hingleung ; Yang, Mengsu ; Cheng, Shukhan ; Fong, Wangfun</creator><creatorcontrib>Lam, Wing ; Chan, Hingleung ; Yang, Mengsu ; Cheng, Shukhan ; Fong, Wangfun</creatorcontrib><description>Here we report that 2-deoxyglucose/Na azide treatment and free/conjugated doxorubicin are synergistic in cell killing. As demonstrated by fluorescence confocal microscopy, KB-V1 cells retained more conjugated doxorubicin than free doxorubicin. Verapamil or 2-deoxyglucose/Na azide enhanced only the retention of the free drug and the small (<70 kDa) conjugates, indicating that P-glycoprotein (P-gp) is not effective against large conjugates. Conjugated doxorubicin was excluded from nuclei. Initially both free and conjugated doxorubicin accumulated in cytoplasmic organelles. Upon 2-deoxyglucose/Na azide treatment, fluorescence labeling of organelles dissipated. Prolonged (24 h) incubation of conjugate-preloaded cells resulted in redistribution of some of the organelle-associated fluorescence to nuclei, suggesting decoupling. The appearance of free doxorubicin was confirmed by capillary electrophoresis. 2-Deoxyglucose/Na azide treatment also retarded decoupling. Our results suggest that energy starvation, in addition to increasing cellular retention of P-gp substrates, may affect cellular fate of conjugated drugs with a possible enhancing effect in cancer cell killing.</description><identifier>ISSN: 0959-4973</identifier><identifier>EISSN: 1473-5741</identifier><identifier>DOI: 10.1097/00001813-199902000-00005</identifier><identifier>PMID: 10211547</identifier><language>eng</language><publisher>England: Lippincott Williams & Wilkins, Inc</publisher><subject>Antineoplastic Agents - pharmacology ; Cell Death - drug effects ; Cell Nucleus - drug effects ; Cell Nucleus - metabolism ; Colchicine - pharmacology ; Deoxyglucose - pharmacology ; Dextrans - pharmacology ; Doxorubicin - metabolism ; Doxorubicin - pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Drug Synergism ; Energy Metabolism ; Humans ; KB Cells - drug effects ; KB Cells - metabolism ; Sodium Azide - pharmacology ; Subcellular Fractions ; Tumor Cells, Cultured ; Vinblastine - pharmacology</subject><ispartof>Anti-cancer drugs, 1999-02, Vol.10 (2), p.171-178</ispartof><rights>1999 Lippincott Williams & Wilkins, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3565-ed39bd74cbb1779e38b08fabca8028d59fbdc17924dece3c5e0a035fdc2827403</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27926,27927</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10211547$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lam, Wing</creatorcontrib><creatorcontrib>Chan, Hingleung</creatorcontrib><creatorcontrib>Yang, Mengsu</creatorcontrib><creatorcontrib>Cheng, Shukhan</creatorcontrib><creatorcontrib>Fong, Wangfun</creatorcontrib><title>Synergism of energy starvation and dextran-conjugated doxorubicin in the killing of multidrug-resistant KB carcinoma cells</title><title>Anti-cancer drugs</title><addtitle>Anticancer Drugs</addtitle><description>Here we report that 2-deoxyglucose/Na azide treatment and free/conjugated doxorubicin are synergistic in cell killing. As demonstrated by fluorescence confocal microscopy, KB-V1 cells retained more conjugated doxorubicin than free doxorubicin. Verapamil or 2-deoxyglucose/Na azide enhanced only the retention of the free drug and the small (<70 kDa) conjugates, indicating that P-glycoprotein (P-gp) is not effective against large conjugates. Conjugated doxorubicin was excluded from nuclei. Initially both free and conjugated doxorubicin accumulated in cytoplasmic organelles. Upon 2-deoxyglucose/Na azide treatment, fluorescence labeling of organelles dissipated. Prolonged (24 h) incubation of conjugate-preloaded cells resulted in redistribution of some of the organelle-associated fluorescence to nuclei, suggesting decoupling. The appearance of free doxorubicin was confirmed by capillary electrophoresis. 2-Deoxyglucose/Na azide treatment also retarded decoupling. Our results suggest that energy starvation, in addition to increasing cellular retention of P-gp substrates, may affect cellular fate of conjugated drugs with a possible enhancing effect in cancer cell killing.</description><subject>Antineoplastic Agents - pharmacology</subject><subject>Cell Death - drug effects</subject><subject>Cell Nucleus - drug effects</subject><subject>Cell Nucleus - metabolism</subject><subject>Colchicine - pharmacology</subject><subject>Deoxyglucose - pharmacology</subject><subject>Dextrans - pharmacology</subject><subject>Doxorubicin - metabolism</subject><subject>Doxorubicin - pharmacology</subject><subject>Drug Resistance, Multiple</subject><subject>Drug Resistance, Neoplasm</subject><subject>Drug Synergism</subject><subject>Energy Metabolism</subject><subject>Humans</subject><subject>KB Cells - drug effects</subject><subject>KB Cells - metabolism</subject><subject>Sodium Azide - pharmacology</subject><subject>Subcellular Fractions</subject><subject>Tumor Cells, Cultured</subject><subject>Vinblastine - pharmacology</subject><issn>0959-4973</issn><issn>1473-5741</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1UctOwzAQtBAIyuMXkH_AYMcxjo-AeAkkDsA5cuxN69ZJkO1Ay9fjUkBcWK20u6OZOcwihBk9YVTJU5qLVYwTppSiRb7IGhJbaMJKyYmQJdtGE6qEIqWSfA_txzjPjIzzXbTHaMGYKOUEfTyteghTFzs8tBjW-wrHpMObTm7ose4ttrBMQffEDP18nOoEGRqWQxgbZ1yPc6cZ4IXz3vXTtU03-uRsGKckQHTZrU_4_gIbHTJ_6DQ24H08RDut9hGOvucBerm-er68JQ-PN3eX5w_EcHEmCFiuGitL0zRMSgW8amjV6sboihaVFaptrGFSFaUFA9wIoJpy0VpTVIUsKT9A1cbXhCHGAG39Glynw6pmtF7HWf_EWf_G-QWJLD3eSF_HpgP7R7jJLxPKDeF98AlCXPjxHUI9A-3TrP7vTfwTQvKDRg</recordid><startdate>199902</startdate><enddate>199902</enddate><creator>Lam, Wing</creator><creator>Chan, Hingleung</creator><creator>Yang, Mengsu</creator><creator>Cheng, Shukhan</creator><creator>Fong, Wangfun</creator><general>Lippincott Williams & Wilkins, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>199902</creationdate><title>Synergism of energy starvation and dextran-conjugated doxorubicin in the killing of multidrug-resistant KB carcinoma cells</title><author>Lam, Wing ; Chan, Hingleung ; Yang, Mengsu ; Cheng, Shukhan ; Fong, Wangfun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3565-ed39bd74cbb1779e38b08fabca8028d59fbdc17924dece3c5e0a035fdc2827403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Antineoplastic Agents - pharmacology</topic><topic>Cell Death - drug effects</topic><topic>Cell Nucleus - drug effects</topic><topic>Cell Nucleus - metabolism</topic><topic>Colchicine - pharmacology</topic><topic>Deoxyglucose - pharmacology</topic><topic>Dextrans - pharmacology</topic><topic>Doxorubicin - metabolism</topic><topic>Doxorubicin - pharmacology</topic><topic>Drug Resistance, Multiple</topic><topic>Drug Resistance, Neoplasm</topic><topic>Drug Synergism</topic><topic>Energy Metabolism</topic><topic>Humans</topic><topic>KB Cells - drug effects</topic><topic>KB Cells - metabolism</topic><topic>Sodium Azide - pharmacology</topic><topic>Subcellular Fractions</topic><topic>Tumor Cells, Cultured</topic><topic>Vinblastine - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lam, Wing</creatorcontrib><creatorcontrib>Chan, Hingleung</creatorcontrib><creatorcontrib>Yang, Mengsu</creatorcontrib><creatorcontrib>Cheng, Shukhan</creatorcontrib><creatorcontrib>Fong, Wangfun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Anti-cancer drugs</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lam, Wing</au><au>Chan, Hingleung</au><au>Yang, Mengsu</au><au>Cheng, Shukhan</au><au>Fong, Wangfun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synergism of energy starvation and dextran-conjugated doxorubicin in the killing of multidrug-resistant KB carcinoma cells</atitle><jtitle>Anti-cancer drugs</jtitle><addtitle>Anticancer Drugs</addtitle><date>1999-02</date><risdate>1999</risdate><volume>10</volume><issue>2</issue><spage>171</spage><epage>178</epage><pages>171-178</pages><issn>0959-4973</issn><eissn>1473-5741</eissn><abstract>Here we report that 2-deoxyglucose/Na azide treatment and free/conjugated doxorubicin are synergistic in cell killing. As demonstrated by fluorescence confocal microscopy, KB-V1 cells retained more conjugated doxorubicin than free doxorubicin. Verapamil or 2-deoxyglucose/Na azide enhanced only the retention of the free drug and the small (<70 kDa) conjugates, indicating that P-glycoprotein (P-gp) is not effective against large conjugates. Conjugated doxorubicin was excluded from nuclei. Initially both free and conjugated doxorubicin accumulated in cytoplasmic organelles. Upon 2-deoxyglucose/Na azide treatment, fluorescence labeling of organelles dissipated. Prolonged (24 h) incubation of conjugate-preloaded cells resulted in redistribution of some of the organelle-associated fluorescence to nuclei, suggesting decoupling. The appearance of free doxorubicin was confirmed by capillary electrophoresis. 2-Deoxyglucose/Na azide treatment also retarded decoupling. Our results suggest that energy starvation, in addition to increasing cellular retention of P-gp substrates, may affect cellular fate of conjugated drugs with a possible enhancing effect in cancer cell killing.</abstract><cop>England</cop><pub>Lippincott Williams & Wilkins, Inc</pub><pmid>10211547</pmid><doi>10.1097/00001813-199902000-00005</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0959-4973 |
| ispartof | Anti-cancer drugs, 1999-02, Vol.10 (2), p.171-178 |
| issn | 0959-4973 1473-5741 |
| language | eng |
| recordid | cdi_crossref_primary_10_1097_00001813_199902000_00005 |
| source | MEDLINE; Journals@Ovid Complete |
| subjects | Antineoplastic Agents - pharmacology Cell Death - drug effects Cell Nucleus - drug effects Cell Nucleus - metabolism Colchicine - pharmacology Deoxyglucose - pharmacology Dextrans - pharmacology Doxorubicin - metabolism Doxorubicin - pharmacology Drug Resistance, Multiple Drug Resistance, Neoplasm Drug Synergism Energy Metabolism Humans KB Cells - drug effects KB Cells - metabolism Sodium Azide - pharmacology Subcellular Fractions Tumor Cells, Cultured Vinblastine - pharmacology |
| title | Synergism of energy starvation and dextran-conjugated doxorubicin in the killing of multidrug-resistant KB carcinoma cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-18T10%3A40%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Synergism%20of%20energy%20starvation%20and%20dextran-conjugated%20doxorubicin%20in%20the%20killing%20of%20multidrug-resistant%20KB%20carcinoma%20cells&rft.jtitle=Anti-cancer%20drugs&rft.au=Lam,%20Wing&rft.date=1999-02&rft.volume=10&rft.issue=2&rft.spage=171&rft.epage=178&rft.pages=171-178&rft.issn=0959-4973&rft.eissn=1473-5741&rft_id=info:doi/10.1097/00001813-199902000-00005&rft_dat=%3Cpubmed_cross%3E10211547%3C/pubmed_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/10211547&rfr_iscdi=true |