Ultrasound-induced hyperthermia increases cellular uptake and cytotoxicity of P-glycoprotein substrates in multi-drug resistant cells
Localized hyperthermia has been shown previously to augment the cytotoxicity of some lipophilic anticancer drugs. Because many of the substrates for the multi-drug resistance (MDR) transporter P-glycoprotein (P-gp) are lipophilic in nature, studies were conducted to test the hypothesis that hyperthe...
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| Veröffentlicht in: | Pharmaceutical research 2001-09, Vol.18 (9), p.1255-1261 |
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| creator | YANG LIU CHO, Cheong-Weon XIANGDONG YAN HENTHORN, Thomas K LILLEHEI, Kevin O COBB, Wesley N NG, Ka-Yun |
| description | Localized hyperthermia has been shown previously to augment the cytotoxicity of some lipophilic anticancer drugs. Because many of the substrates for the multi-drug resistance (MDR) transporter P-glycoprotein (P-gp) are lipophilic in nature, studies were conducted to test the hypothesis that hyperthermia induced by ultrasound could also increase cellular uptake and cytotoxicity of P-gp substrates by P-gp-expressing cells.
To test this hypothesis, we studied the effects of hyperthermia and ultrasound on cellular accumulation of putative P-gp substrates, rhodamine 123 (R123) and doxorubicin (DOX), and cytotoxicity of DOX in the parent and MDR variants of two human cancer cell lines.
Treatment of cells with hyperthermia or ultrasound (20 min at 41 degrees C) both caused a significant increase over controls (no ultrasound treatment) in R123 and DOX accumulation in the parent and MDR lines of MV522 and KB cells. Ultrasound also substantially increased the antiproliferative effects of DOX in both the parent and MDR variants of MV522 and KB cell lines when compared with controls. Our results also indicated that ultrasound exerted a much greater effect on cellular accumulation of R123 and DOX and cytotoxicity enhancement of DOX in the MDR variants than putative P-gp antagonist such as verapamil.
The present results point to the potential use of ultrasound-induced hyperthermia as a much safer alternative to P-gp antagonist for reversal of MDR. |
| doi_str_mv | 10.1023/a:1013025625156 |
| format | Article |
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To test this hypothesis, we studied the effects of hyperthermia and ultrasound on cellular accumulation of putative P-gp substrates, rhodamine 123 (R123) and doxorubicin (DOX), and cytotoxicity of DOX in the parent and MDR variants of two human cancer cell lines.
Treatment of cells with hyperthermia or ultrasound (20 min at 41 degrees C) both caused a significant increase over controls (no ultrasound treatment) in R123 and DOX accumulation in the parent and MDR lines of MV522 and KB cells. Ultrasound also substantially increased the antiproliferative effects of DOX in both the parent and MDR variants of MV522 and KB cell lines when compared with controls. Our results also indicated that ultrasound exerted a much greater effect on cellular accumulation of R123 and DOX and cytotoxicity enhancement of DOX in the MDR variants than putative P-gp antagonist such as verapamil.
The present results point to the potential use of ultrasound-induced hyperthermia as a much safer alternative to P-gp antagonist for reversal of MDR.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1023/a:1013025625156</identifier><identifier>PMID: 11683237</identifier><identifier>CODEN: PHREEB</identifier><language>eng</language><publisher>New York, NY: Springer</publisher><subject>Antibiotics, Antineoplastic - metabolism ; Antibiotics, Antineoplastic - toxicity ; Antineoplastic agents ; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism ; Biological and medical sciences ; Calcium Channel Blockers - pharmacology ; Cancer therapies ; Cell Division - drug effects ; Cell Survival - drug effects ; Cytotoxicity ; Doxorubicin - metabolism ; Doxorubicin - toxicity ; Drug resistance ; Drug Resistance, Multiple - radiation effects ; Drug Resistance, Neoplasm ; Fever ; General aspects ; Glycoproteins ; Humans ; Hyperthermia ; Hyperthermia, Induced - methods ; Hypotheses ; Medical sciences ; Pharmacology. Drug treatments ; Radiation ; Rhodamine 123 - metabolism ; Rhodamine 123 - toxicity ; Temperature ; Tumor Cells, Cultured ; Tumors ; Ultrasonic imaging ; Ultrasonic Therapy ; Verapamil - pharmacology</subject><ispartof>Pharmaceutical research, 2001-09, Vol.18 (9), p.1255-1261</ispartof><rights>2002 INIST-CNRS</rights><rights>Copyright Kluwer Academic Publishers Sep 2001</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14066495$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11683237$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>YANG LIU</creatorcontrib><creatorcontrib>CHO, Cheong-Weon</creatorcontrib><creatorcontrib>XIANGDONG YAN</creatorcontrib><creatorcontrib>HENTHORN, Thomas K</creatorcontrib><creatorcontrib>LILLEHEI, Kevin O</creatorcontrib><creatorcontrib>COBB, Wesley N</creatorcontrib><creatorcontrib>NG, Ka-Yun</creatorcontrib><title>Ultrasound-induced hyperthermia increases cellular uptake and cytotoxicity of P-glycoprotein substrates in multi-drug resistant cells</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><description>Localized hyperthermia has been shown previously to augment the cytotoxicity of some lipophilic anticancer drugs. Because many of the substrates for the multi-drug resistance (MDR) transporter P-glycoprotein (P-gp) are lipophilic in nature, studies were conducted to test the hypothesis that hyperthermia induced by ultrasound could also increase cellular uptake and cytotoxicity of P-gp substrates by P-gp-expressing cells.
To test this hypothesis, we studied the effects of hyperthermia and ultrasound on cellular accumulation of putative P-gp substrates, rhodamine 123 (R123) and doxorubicin (DOX), and cytotoxicity of DOX in the parent and MDR variants of two human cancer cell lines.
Treatment of cells with hyperthermia or ultrasound (20 min at 41 degrees C) both caused a significant increase over controls (no ultrasound treatment) in R123 and DOX accumulation in the parent and MDR lines of MV522 and KB cells. Ultrasound also substantially increased the antiproliferative effects of DOX in both the parent and MDR variants of MV522 and KB cell lines when compared with controls. Our results also indicated that ultrasound exerted a much greater effect on cellular accumulation of R123 and DOX and cytotoxicity enhancement of DOX in the MDR variants than putative P-gp antagonist such as verapamil.
The present results point to the potential use of ultrasound-induced hyperthermia as a much safer alternative to P-gp antagonist for reversal of MDR.</description><subject>Antibiotics, Antineoplastic - metabolism</subject><subject>Antibiotics, Antineoplastic - toxicity</subject><subject>Antineoplastic agents</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism</subject><subject>Biological and medical sciences</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Cancer therapies</subject><subject>Cell Division - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Cytotoxicity</subject><subject>Doxorubicin - metabolism</subject><subject>Doxorubicin - toxicity</subject><subject>Drug resistance</subject><subject>Drug Resistance, Multiple - radiation effects</subject><subject>Drug Resistance, Neoplasm</subject><subject>Fever</subject><subject>General aspects</subject><subject>Glycoproteins</subject><subject>Humans</subject><subject>Hyperthermia</subject><subject>Hyperthermia, Induced - methods</subject><subject>Hypotheses</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Radiation</subject><subject>Rhodamine 123 - metabolism</subject><subject>Rhodamine 123 - toxicity</subject><subject>Temperature</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><subject>Ultrasonic imaging</subject><subject>Ultrasonic Therapy</subject><subject>Verapamil - pharmacology</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpFkE1r20AQhpfQkDhuzrmVJdCjmtlPrXorJm0KgeSQQG9mtTuy15Uldz8g-gH53xGtQ0_DwDPPzLyEXDH4woCLG_uVARPAleaKKX1CFkzVompA_vpAFlBzWZlasnNykdIOAAxr5Bk5Z0wbwUW9IK_PfY42jWXwVRh8cejpdjpgzFuM-2BpGFxEmzBRh31fehtpOWT7G6kdPHVTHvP4ElzIEx07-lht-smNhzhmDANNpU2zPs_Tc7cvfQ6Vj2VDI6aQsh3yX2v6SE472ye8PNYlefp--7S6q-4ffvxcfbuvdkJArox0LdSKN8q2jcdWKV9r1mg0THtpWsXnx2o0imMLBroODYBSHAwCSC6W5Pqfdr7vT8GU17uxxGHeuOac60byOZYl-XSESrtHvz7EsLdxWr9nNgOfj4BNzvZdtIML6T8nQWvZKPEG9lV9mg</recordid><startdate>20010901</startdate><enddate>20010901</enddate><creator>YANG LIU</creator><creator>CHO, Cheong-Weon</creator><creator>XIANGDONG YAN</creator><creator>HENTHORN, Thomas K</creator><creator>LILLEHEI, Kevin O</creator><creator>COBB, Wesley N</creator><creator>NG, Ka-Yun</creator><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20010901</creationdate><title>Ultrasound-induced hyperthermia increases cellular uptake and cytotoxicity of P-glycoprotein substrates in multi-drug resistant cells</title><author>YANG LIU ; CHO, Cheong-Weon ; XIANGDONG YAN ; HENTHORN, Thomas K ; LILLEHEI, Kevin O ; COBB, Wesley N ; NG, Ka-Yun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-j330t-84cb075295ab9deb55d76196e816d48b521167e852eb080ffe80055208e00423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Antibiotics, Antineoplastic - metabolism</topic><topic>Antibiotics, Antineoplastic - toxicity</topic><topic>Antineoplastic agents</topic><topic>ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism</topic><topic>Biological and medical sciences</topic><topic>Calcium Channel Blockers - pharmacology</topic><topic>Cancer therapies</topic><topic>Cell Division - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Cytotoxicity</topic><topic>Doxorubicin - metabolism</topic><topic>Doxorubicin - toxicity</topic><topic>Drug resistance</topic><topic>Drug Resistance, Multiple - radiation effects</topic><topic>Drug Resistance, Neoplasm</topic><topic>Fever</topic><topic>General aspects</topic><topic>Glycoproteins</topic><topic>Humans</topic><topic>Hyperthermia</topic><topic>Hyperthermia, Induced - methods</topic><topic>Hypotheses</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Radiation</topic><topic>Rhodamine 123 - metabolism</topic><topic>Rhodamine 123 - toxicity</topic><topic>Temperature</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><topic>Ultrasonic imaging</topic><topic>Ultrasonic Therapy</topic><topic>Verapamil - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>YANG LIU</creatorcontrib><creatorcontrib>CHO, Cheong-Weon</creatorcontrib><creatorcontrib>XIANGDONG YAN</creatorcontrib><creatorcontrib>HENTHORN, Thomas K</creatorcontrib><creatorcontrib>LILLEHEI, Kevin O</creatorcontrib><creatorcontrib>COBB, Wesley N</creatorcontrib><creatorcontrib>NG, Ka-Yun</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>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database (ProQuest)</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest - Health & Medical Complete保健、医学与药学数据库</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>YANG LIU</au><au>CHO, Cheong-Weon</au><au>XIANGDONG YAN</au><au>HENTHORN, Thomas K</au><au>LILLEHEI, Kevin O</au><au>COBB, Wesley N</au><au>NG, Ka-Yun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ultrasound-induced hyperthermia increases cellular uptake and cytotoxicity of P-glycoprotein substrates in multi-drug resistant cells</atitle><jtitle>Pharmaceutical research</jtitle><addtitle>Pharm Res</addtitle><date>2001-09-01</date><risdate>2001</risdate><volume>18</volume><issue>9</issue><spage>1255</spage><epage>1261</epage><pages>1255-1261</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><coden>PHREEB</coden><abstract>Localized hyperthermia has been shown previously to augment the cytotoxicity of some lipophilic anticancer drugs. Because many of the substrates for the multi-drug resistance (MDR) transporter P-glycoprotein (P-gp) are lipophilic in nature, studies were conducted to test the hypothesis that hyperthermia induced by ultrasound could also increase cellular uptake and cytotoxicity of P-gp substrates by P-gp-expressing cells.
To test this hypothesis, we studied the effects of hyperthermia and ultrasound on cellular accumulation of putative P-gp substrates, rhodamine 123 (R123) and doxorubicin (DOX), and cytotoxicity of DOX in the parent and MDR variants of two human cancer cell lines.
Treatment of cells with hyperthermia or ultrasound (20 min at 41 degrees C) both caused a significant increase over controls (no ultrasound treatment) in R123 and DOX accumulation in the parent and MDR lines of MV522 and KB cells. Ultrasound also substantially increased the antiproliferative effects of DOX in both the parent and MDR variants of MV522 and KB cell lines when compared with controls. Our results also indicated that ultrasound exerted a much greater effect on cellular accumulation of R123 and DOX and cytotoxicity enhancement of DOX in the MDR variants than putative P-gp antagonist such as verapamil.
The present results point to the potential use of ultrasound-induced hyperthermia as a much safer alternative to P-gp antagonist for reversal of MDR.</abstract><cop>New York, NY</cop><pub>Springer</pub><pmid>11683237</pmid><doi>10.1023/a:1013025625156</doi><tpages>7</tpages></addata></record> |
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| subjects | Antibiotics, Antineoplastic - metabolism Antibiotics, Antineoplastic - toxicity Antineoplastic agents ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism Biological and medical sciences Calcium Channel Blockers - pharmacology Cancer therapies Cell Division - drug effects Cell Survival - drug effects Cytotoxicity Doxorubicin - metabolism Doxorubicin - toxicity Drug resistance Drug Resistance, Multiple - radiation effects Drug Resistance, Neoplasm Fever General aspects Glycoproteins Humans Hyperthermia Hyperthermia, Induced - methods Hypotheses Medical sciences Pharmacology. Drug treatments Radiation Rhodamine 123 - metabolism Rhodamine 123 - toxicity Temperature Tumor Cells, Cultured Tumors Ultrasonic imaging Ultrasonic Therapy Verapamil - pharmacology |
| title | Ultrasound-induced hyperthermia increases cellular uptake and cytotoxicity of P-glycoprotein substrates in multi-drug resistant cells |
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