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CHANGES IN PLASMA MEMBRANE FLUIDITY OF IMMORTAL RODENT CELLS INDUCED BY ANTICANCER DRUGS DOXORUBICIN, ACLARUBICIN AND MITOXANTRONE

✍ Scribed by Malgorzata Jedrzejczak; Aneta Koceva-Chyla; Krzysztof Gwozdzinski; Zofia Józwiak


Publisher
Elsevier Science
Year
1999
Tongue
English
Weight
160 KB
Volume
23
Category
Article
ISSN
1065-6995

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✦ Synopsis


The aim of this study was to examine the effect of three structurally different anticancer drugs-the pro-oxidative anthracyclines doxorubicin (DOX) and aclarubicin (ACL), and antioxidative anthraquinone mitoxantrone (MTX) on the fluidity of plasma membrane of immortalized rodent fibroblasts using fluorescence spectroscopy and electron spin resonance (ESR) techniques. Two kinds of fluorescent probes (TMA-DPH and 12-AS) and spin labels (5-DS and methyl-12-DS) were used to monitor fluidity in the hydrophobic core and in the polar headgroup region of the lipid bilayer. Immortalized hamster B14 and NIH 3T3 mouse fibroblasts were exposed to DOX, ACL and MTX. We demonstrate that these drugs influence predominantly the hydrophobic core of the lipid bilayer, inducing significant decrease in its fluidity at low concentrations (2-5 microM). A decreased membrane fluidity at the surface of the lipid bilayer was observed only at a higher concentration (20 microM) of the drugs, which indicates that DOX, ACL and MTX intercalate mainly into the hydrophobic core of the membrane, thereby perturbing its structure.