Enhancement of anthracycline and alkylator cytotoxicity by ethacrynic acid in primary cultures of human tissues

Ethacrynic acid [2,3-dichloro-4-(2-methylene-1-oxobutyl)phenoxyl] acetic acid, is a water-soluble diuretic agent that has been shown to potentiate the in vitro cytotoxicity of chemotherapeutic agents in established cell lines. We used the differential staining cytotoxicity (DiSC) assay to determine...

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Veröffentlicht in:Cancer chemotherapy and pharmacology 1990-01, Vol.26 (5), p.318-322
Hauptverfasser: NAGOURNEY, R. A, MESSENGER, J. C, KERN, D. H, WEISENTHAL, L. M
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container_issue 5
container_start_page 318
container_title Cancer chemotherapy and pharmacology
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creator NAGOURNEY, R. A
MESSENGER, J. C
KERN, D. H
WEISENTHAL, L. M
description Ethacrynic acid [2,3-dichloro-4-(2-methylene-1-oxobutyl)phenoxyl] acetic acid, is a water-soluble diuretic agent that has been shown to potentiate the in vitro cytotoxicity of chemotherapeutic agents in established cell lines. We used the differential staining cytotoxicity (DiSC) assay to determine whether ethacrynic acid at 1 and 3.3 microM would potentiate the cytotoxicity of nitrogen mustard and/or doxorubicin in primary cultures of hematologic neoplasms from heavily pretreated patients and in normal peripheral blood lymphocytes. At 3.3 microM, ethacrynic acid was toxic to 8 of 24 (33%) tumor specimens studied. In subsequent studies, ethacrynic acid at 1 microM was toxic to only 2 of 54 (4%) tumor specimens. Significant enhancement for doxorubicin or nitrogen mustard was confined to lymphatic malignancies and to normal peripheral blood lymphocytes. Interspecimen variability was observed, with no enhancement in most individual specimens, 2-fold enhancement in some specimens, and 4-fold enhancement in occasional specimens. Clinical trials will be required to determine whether the observed in vitro activity for ethacrynic acid is associated with clinical benefit in unselected or assay-selected patients.
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Significant enhancement for doxorubicin or nitrogen mustard was confined to lymphatic malignancies and to normal peripheral blood lymphocytes. Interspecimen variability was observed, with no enhancement in most individual specimens, 2-fold enhancement in some specimens, and 4-fold enhancement in occasional specimens. 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At 3.3 microM, ethacrynic acid was toxic to 8 of 24 (33%) tumor specimens studied. In subsequent studies, ethacrynic acid at 1 microM was toxic to only 2 of 54 (4%) tumor specimens. Significant enhancement for doxorubicin or nitrogen mustard was confined to lymphatic malignancies and to normal peripheral blood lymphocytes. Interspecimen variability was observed, with no enhancement in most individual specimens, 2-fold enhancement in some specimens, and 4-fold enhancement in occasional specimens. 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Drug treatments</topic><topic>Staining and Labeling</topic><topic>Tumor Cells, Cultured - drug effects</topic><topic>Tumor Cells, Cultured - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>NAGOURNEY, R. A</creatorcontrib><creatorcontrib>MESSENGER, J. C</creatorcontrib><creatorcontrib>KERN, D. H</creatorcontrib><creatorcontrib>WEISENTHAL, L. M</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><jtitle>Cancer chemotherapy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>NAGOURNEY, R. A</au><au>MESSENGER, J. C</au><au>KERN, D. H</au><au>WEISENTHAL, L. M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enhancement of anthracycline and alkylator cytotoxicity by ethacrynic acid in primary cultures of human tissues</atitle><jtitle>Cancer chemotherapy and pharmacology</jtitle><addtitle>Cancer Chemother Pharmacol</addtitle><date>1990-01-01</date><risdate>1990</risdate><volume>26</volume><issue>5</issue><spage>318</spage><epage>322</epage><pages>318-322</pages><issn>0344-5704</issn><eissn>1432-0843</eissn><coden>CCPHDZ</coden><abstract>Ethacrynic acid [2,3-dichloro-4-(2-methylene-1-oxobutyl)phenoxyl] acetic acid, is a water-soluble diuretic agent that has been shown to potentiate the in vitro cytotoxicity of chemotherapeutic agents in established cell lines. 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subjects Antineoplastic agents
Biological and medical sciences
Cell Survival - drug effects
Doxorubicin - pharmacology
Drug Screening Assays, Antitumor - methods
Drug Synergism
Ethacrynic Acid - pharmacology
General aspects
Humans
Leukemia - pathology
Lymphocytes - drug effects
Lymphocytes - pathology
Lymphoma - pathology
Mechlorethamine - pharmacology
Medical sciences
Pharmacology. Drug treatments
Staining and Labeling
Tumor Cells, Cultured - drug effects
Tumor Cells, Cultured - pathology
title Enhancement of anthracycline and alkylator cytotoxicity by ethacrynic acid in primary cultures of human tissues
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