Fatty Acid Composition and Metabolism of Tumor Cells Rendered Resistant to the Anticancer Drug Doxorubicin
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.
KeywordsFatty Acid Methyl Ester Desaturase Acti Essential Fatty Acid Deficiency Ehrlich Ascites Tumor Cell Eicosatrienoic Acid
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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© Plenum Press, New York 1986