Cross-resistance pattern of cell lines selected for resistance towards different cytotoxic drugs to membrane-toxic phospholipids in vitro

  • Andreas W. Himmelmann
  • Susanne Danhauser-Riedl
  • Gabriela Steinhauser
  • Raymonde Busch
  • Edward J. Modest
  • Alessandro Noseda
  • Johann Rastetter
  • W. Ralph Vogler
  • Wolfgang E. Berdel


The synthetic ether lipids ET-18-OCH3 and BM41.440 and a derivative, hexadecylphosphocholine, were tested for inhibition of [3H]-thymidine uptake into a Chinese hamster ovarian cell line (AUXB1) and its multidrug-resistant subline selected for colchicine resistance (CHRC5). The activity of all three compounds against the multidrug-resistant subline was equal to or higher than that against the parent line. The same result was found for their activity against a human leukemic lymphoblastic cell line (CEM/O) and its methotrexate-resistant subline (CEM/MTX). In contrast, two multidrug-resistant cell lines selected for resistance to Adriamycin, the mouse leukemia cell line P388/ADR and the murine sarcoma cell line S180/ADR, expressed modest cross-resistance to the lipids as measured by thymidine uptake. Experiments performed using the trypan-blue dye-exclusion assay yielded comparable results, although this system revealed a slightly different sensitivity in showing the cytotoxicity of the drugs. By this assay, modest cross-resistance for ET-18-OCH3 and BM41.440 to Adriamycin was found only after 24 h incubation and decreased after 48 h incubation, with almost equal sensitivity to both drugs being shown by the parental (P388/W) and resistant lines (P388/ADR). Furthermore, findings from a human tumor-cloning assay were in accordance with these data, although they did not indicate cross-resistance for the P388/ADR cell line. These results suggest that certain ether lipids and derivatives might represent valuable anticancer drugs warranting further study in the setting of resistant disease.


Resistant Cell Line Ether Lipid Thymidine Uptake Hexadecylphosphocholine Chinese Hamster Ovary Line 
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Abbreviations used


alkyl-lysophospholipid derivative(s)


thioether-lysophospholipid derivative(s)


ether lipid(s)






multiple drug resistance




dihydrofolate reductase




fetal calf serum


human tumor-cloning assay


drug concentration inhibiting the 48 h [3H]-thymidine uptake of cells by 50% or resulting in a 50% decrease in trypan-blue dye exclusion or colony formation in the HTCA at the times indicated


relative drug resistance


hexadecylphosphocholine (D18 506)


protein kinase C




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Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • Andreas W. Himmelmann
    • 1
  • Susanne Danhauser-Riedl
    • 1
  • Gabriela Steinhauser
    • 1
  • Raymonde Busch
    • 1
  • Edward J. Modest
    • 2
  • Alessandro Noseda
    • 2
  • Johann Rastetter
    • 1
  • W. Ralph Vogler
    • 3
  • Wolfgang E. Berdel
    • 1
  1. 1.Division of Hematology and Oncology, Department of Medicine I and Department of Medical Statistics and Epidemiology (R.B.)Technische Universität MünchenMünchen 80Federal Republic of Germany
  2. 2.Department of Biochemistry, Bowman Gray School of MedicineWake Forest UniversityWinston-SalemUSA
  3. 3.Division of Hematology and Oncology, Department of MedicineEmory UniversityAtlantaUSA

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