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Megestrol acetate reverses multidrug resistance and interacts with P-glycoprotein

  • Original Articles
  • Megestrol, Multidrug Resistance, P-Glycoprotein
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Summary

We evaluated the multidrug resistance (MDR)-modulating effects of progesterone (PRG) and an orally active, structurally related compound, megestrol acetate (MA), in several MDR human cell lines. At 100 μm, both steroids inhibited the binding of aVinca alkaloid photoaffinity analog to P-glycoprotein (P-gp) in MDR human neuroblastic SH-SY5Y/VCR cells [which show >1500-fold resistance to vincristine (VCR) in the tetrazolium dye (MTT) assay]. However, 100 μm MA markedly enhanced the binding of [3H]-azidopine to P-gp in both SH-SY5Y/VCR cells and the MDR human epidermoid KB-GSV2 cell line (which displays 250-fold resistance to VCR in the MTT assay). PRG had little effect on the binding of [3H]-azidopine to P-gp. MA at low doses was more effective than PRG in sensitizing cells to VCR and enhancing their accumulation of [3H]-VCR. The highly resistant SH-SY5Y/VCR subline exhibited significant collateral sensitivity to both steroids. These data suggest that MA may be a clinically useful modulator of MDR.

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Authors and Affiliations

  1. Section of Hematology/Oncology, University of Chicago Medical Center, 5841 S. Maryland Ave., MC 2115, 60637, Chicago, IL, USA

    Gini F. Fleming, Jacqueline M. Amato, Michael Agresti & Ahmad R. Safa

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  1. Gini F. Fleming
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  2. Jacqueline M. Amato
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  3. Michael Agresti
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  4. Ahmad R. Safa
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Additional information

This work was supported by NIH grant CA-47652. The first author (G. E. F.) was supported by PHS grant DK07134-15

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Fleming, G.F., Amato, J.M., Agresti, M. et al. Megestrol acetate reverses multidrug resistance and interacts with P-glycoprotein. Cancer Chemother. Pharmacol. 29, 445–449 (1992). https://doi.org/10.1007/BF00684845

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  • DOI: https://doi.org/10.1007/BF00684845

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