Fatty Acid Composition and Metabolism of Tumor Cells Rendered Resistant to the Anticancer Drug Doxorubicin

  • J. Robert
  • P. Vrignaud
  • D. Montaudon
  • D. Londos-Gagliardi
Part of the NATO ASI Series book series (NSSA, volume 116)


Anthracyclines are a family of anticancer drugs acting by intercalation between base pairs of DNA and inhibiting therefore macromolecular synthesis. The main compound of the series is called doxorubicin or adriamycin and is widely used in the treatment of hematological malignancies and solid tumors (1). Numerous authors have developped cell culture models of resistance to doxorubicin or its analogue daunorubicin (2). Most of them are obtained by continuous exposure of the cells to the drug, beginning with low, infratoxic concentrations, which are then progressively increased to very high concentrations. Nearly all the cells lines that have been rendered resistant to doxorubicin incorporate much less amounts of the drug than the parental cell lines. This decrease of drug incorporation in resistant cells is mainly due to a striking increase of drug efflux out of the cell, this efflux being an active transport (3) or a passive diffusion (4). Membrane lipids may be of importance in the phenomenon of resistance, whatever the mechanism of the efflux is : either they may intervene as the environment of the carrier and modulate its activity, or they may intervene in regulating membrane permeability. In a work by Ramu et al. (5) a small difference in the sphingomyelin/phosphatidylcholine ratio between sensitive and resistant cells was noticed in P388 leukemia cells and could be due to a lower phosphocholine transferase activity in resistant cells. The fatty acid composition of the two lines was however not studied in this paper. The membrane fluidity of resistant cells has been shown to decrease by authors working on different cell lines (6, 7) but none of the papers makes a proposal about the lipid modification that could underlie such a modification of membrane fluidity.


Fatty Acid Methyl Ester Desaturase Acti Essential Fatty Acid Deficiency Ehrlich Ascites Tumor Cell Eicosatrienoic Acid 
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  1. 1.
    R.C. Young, R.F. Ozols and C.E. Myers, The anthracycline antineoplastic drugs, N. Engl.J. Med. 305: 139 (1981).PubMedCrossRefGoogle Scholar
  2. 2.
    S. Kaye and S. Merry, Tumour cell resistance to anthracyclines: a review, Cancer Chemother. Pharmacol. 14: 96 (1985).PubMedCrossRefGoogle Scholar
  3. 3.
    K. Dano, Active outward transport of daunomycin in resistant Ehrlich ascites tumor cells, Biochim. biophys. Acta 323: 466 (1973).PubMedCrossRefGoogle Scholar
  4. 4.
    J.M. Siegfried, T.G. Burke and T.R. Tritton, Cellular transport of anthracyclines by passive diffusion; implications for drug resistance, Biochem. Pharmacol. 34: 593 (1985).PubMedCrossRefGoogle Scholar
  5. 5.
    A. Ramu, D. Glaubiger and H. Weintraub, Differences in lipid composition of doxorubicin-sensitive and -resistant P388 cells, Cancer Treat. Rep. 68: 637 (1984).PubMedGoogle Scholar
  6. 6.
    A. Ramu, D. Glaubiger, I.T. Magrath and A. Joshi, Plasma membrane lipid structural order in doxorubicin-sensitive and -resistant P388 cells, Cancer Res. 43: 5533 (1983).PubMedGoogle Scholar
  7. 7.
    D.A. Rintoul and M.S. Center, Involvement of plasma membrane lipid structural order in adriamycin resistance in Chinese hamster lung cells, Cancer Res. 44: 4978 (1984).PubMedGoogle Scholar
  8. 8.
    P. Vrignaud, D. Londos-Gagliardi and J. Robert, Cellular pharmacology of doxorubicin in sensitive and resistant rat glioblastoma cells in culture, Oncology (in the press).Google Scholar
  9. 9.
    P. Benda, J. Lightbody, G. Sato, L. Levine and W. Sweet, Differentiated rat glial cell strain in tissue culture, Science 161: 370 (1968).PubMedCrossRefGoogle Scholar
  10. 10.
    J. Folch, M. Lees and G. Sloane-Stanley, A simple method for the isolation and purification of total lipids from animal tissues, J. biol. Chem. 226: 397 (1957).Google Scholar
  11. 11.
    D.R. Idler and C.A. Baumann, Skin sterols. III. Sterol structure and the Liebermann-Burchard reaction, J. biol. Chem. 203: 389 (1953).PubMedGoogle Scholar
  12. 12.
    M. Macheboeuf and J. Delsal, Sur le dosage de très petites quantités de phosphore dans les matières organiques, Bull. Soc. Chim. biol. 25: 116 (1943).Google Scholar
  13. 13.
    E. Yavin and A. Zutra, Separation and analysis of [32P]-labeled phospholipids by a simple and rapid thin-layer chromatographic procedure and its application to cultured neuroblastoma cells, Anal. Biochem. 80: 430 (1977).PubMedCrossRefGoogle Scholar
  14. 14.
    D. Montaudon, J.C. Louis and J. Robert, Phospholipid acyl group composition in normal and tumoral glial cells in culture, Lipids 16: 293 (1981).PubMedCrossRefGoogle Scholar
  15. 15.
    J. Robert, D. Montaudon and P. Hugues, Incorporation and metabolism of exogenous fatty acids by cultured normal and tumoral glial cells, Biochim. biophys. Acta 752: 383 (1983).PubMedCrossRefGoogle Scholar
  16. 16.
    L.L. Stoll and A.A. Spector, Changes in serum influence the fatty acid composition of established cell lines, In vitro 20: 732 (1984).PubMedCrossRefGoogle Scholar
  17. 17.
    J. Robert, P. Mandel and G. Rebel, Membrane lipids in bromodeoxyuridine differentiated astroglial cells in culture, Lipids 14: 852 (1979).PubMedCrossRefGoogle Scholar
  18. 18.
    J. Robert, G. Rebel and P. Mandel, Essential fatty acid metabolism in cultured astroblasts, Biochimie 59: 417 (1977).PubMedCrossRefGoogle Scholar
  19. 19.
    E.L. Pugh and M. Kates, The dietary regulation of acyltransferase and desaturase activities in microsomal membranes of rat liver, Lipids 19: 48 (1984).PubMedCrossRefGoogle Scholar
  20. 20.
    J. Storch and D. Schachter, Dietary induction of acyl chain desaturases alters the lipid composition and fluidity of rat hepatocyte plasma membrane, Biochemistry 23: 1165 (1984).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • J. Robert
    • 1
    • 2
  • P. Vrignaud
    • 1
    • 2
  • D. Montaudon
    • 1
    • 2
  • D. Londos-Gagliardi
    • 1
    • 2
  1. 1.Fondation BergoniéBordeaux CédexFrance
  2. 2.Université de Bordeaux IIBordeaux CédexFrance

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