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Doxorubicin-transferrin conjugate selectively overcomes multidrug resistance in leukaemia cells

Cellular & Molecular Biology Letters volume 14, pages 113–127 (2009)Cite this article

Abstract

Neoplastic cells frequently have an increased number of transferrin receptors. Coupling transferrin to an anti-neoplastic drug has the potential to overcome multidrug resistance (MDR). The purpose of this study was to examine the distribution and action of doxorubicin-transferrin conjugate (DOXTRF) in a leukaemia cell line (HL60), a multidrug-resistant leukaemia cell line (HL60ADR) and a normal tissue cell line (human fibroblasts). The intracellular accumulation of DOX and DOX-TRF was monitored by direct fluorescence. More DOX-TRF than free DOX was delivered to the tumour cells, and consecutively the levels of DNA double-strand breaks and apoptosis increased even in the multidrug-resistant cell line. In the normal tissue cell line, DOX-TRF did not accumulate, and therefore, the levels of DNA double-strand breaks and apoptosis did not increase. Cell viability was determined using the MTT assay. The IC50 for DOX-TRF was lower than the IC50 value for the free drug in both leukaemia cell lines. The IC50 values for the HL60 cells were 0.08 μM for DOX and 0.02 μM for DOX-TRF. The IC50 values for HL60ADR cells were 7 μM for DOX and 0.035 μM for DOX-TRF. In conclusion, DOX-TRF was able to overcome MDR in the leukaemia cell lines while having only a very limited effect on normal tissue cells.

Abbreviations

DOX:

doxorubicin

DOX-TRF:

doxorubicin-transferrin conjugate

MDR:

multidrug resistance

MTT:

3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide

SD:

standard deviation

SDS:

sodium dodecyl sulfate

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Authors and Affiliations

  1. Department of Radiation Oncology, Friedrich-Alexander-University Erlangen-Nuremberg, Universitätsstr. 27, D-91054, Erlangen, Germany

    Dorota Łubgan, Gerhard G. Grabenbauer & Luitpold V. R. Distel

  2. Department of Thermobiology, University of Łódź, Banacha 12/16, 90-237, Łódź, Poland

    Zofia Jóźwiak

Authors
  1. Dorota Łubgan
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  2. Zofia Jóźwiak
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  3. Gerhard G. Grabenbauer
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  4. Luitpold V. R. Distel
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Correspondence to Dorota Łubgan.

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Łubgan, D., Jóźwiak, Z., Grabenbauer, G.G. et al. Doxorubicin-transferrin conjugate selectively overcomes multidrug resistance in leukaemia cells. Cell Mol Biol Lett 14, 113–127 (2009). https://doi.org/10.2478/s11658-008-0037-2

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Cellular & Molecular Biology Letters

ISSN: 1689-1392

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