Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies

Henrietta Nagy, Katalin Goda, Ferenc Fenyvesi, Zsolt Bacsó, Mária Szilasi, János Kappelmayer, György Lustyik, Maurizio Cianfriglia, Gábor Szabó

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27 Citations (Scopus)

Abstract

P-glycoprotein (Pgp) is one of the ABC transporters responsible for the multidrug resistance of cancer cells. The conformational changes of Pgp that occur in the presence of substrates/modulators or ATP depletion are accompanied by the up-shift of UIC2 monoclonal antibody (mAb) binding. In the case of cyclosporin A, vinblastine or valinomycin, this up-shift was found to be concomitant with the near-complete suppression of labeling with other mAbs specific for Pgp epitopes overlapping with UIC2, while pre-treatment with verapamil or Tween 80 brings about a modest suppression. Here we have extended these observations to 44 Pgp interacting agents, and found that only 8 fall into the cyclosporin-like category, inducing a conformational state characterized by the complete UIC2 dominance. The rest of the drugs either did not affect antibody competition or had a modest effect. Thus, Pgp substrates/modulators can be classified into distinct modalities based on the conformational change they elicit.

Original languageEnglish
Pages (from-to)942-949
Number of pages8
JournalBiochemical and biophysical research communications
Volume315
Issue number4
DOIs
Publication statusPublished - Mar 19 2004

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Keywords

  • Conformation
  • Multidrug resistance
  • P-glycoprotein
  • Substrate
  • UIC2

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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