Megestrol acetate reverses multidrug resistance and interacts with P-glycoprotein

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

Research output: Contribution to journalArticle

56 Scopus citations


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 a Vinca 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.

Original languageEnglish (US)
Pages (from-to)445-449
Number of pages5
JournalCancer Chemotherapy and Pharmacology
Issue number6
StatePublished - Nov 1 1992
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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