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Cancer Chemotherapy and Pharmacology

, Volume 26, Issue 5, pp 318–322 | Cite as

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

  • Robert A. Nagourney
  • John C. Messenger
  • David H. Kern
  • Larry M. Weisenthal
Article

Summary

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 µM 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 µM, ethacrynic acid was toxic to 8 of 24 (33%) tumor specimens studied. In subsequent studies, ethacrynic acid at 1 µM 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.

Keywords

Chronic Lymphocytic Leukemia Chronic Lymphocytic Leukemia Cell Ethacrynic Acid Nitrogen Mustard Buthionine Sulfoximine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • Robert A. Nagourney
    • 1
    • 2
    • 3
  • John C. Messenger
    • 1
    • 2
  • David H. Kern
    • 1
  • Larry M. Weisenthal
    • 1
  1. 1.Oncotech Inc.Irvine
  2. 2.The Memorial Cancer InstituteLong Beach
  3. 3.Division of Hematology/Oncology, Department of MedicineThe University of CaliforniaIrvineUSA

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