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Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies |
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| Authors: | Nagy Henrietta Goda Katalin Fenyvesi Ferenc Bacsó Zsolt Szilasi Mária Kappelmayer János Lustyik György Cianfriglia Maurizio Szabó Gábor |
| Institution: | a Department of Biophysics and Cell Biology, University of Debrecen, Debrecen, Hungary b Department of Pharmaceutical Technology, University of Debrecen, Debrecen, Hungary c Clinic of Pulmonology, University of Debrecen, Debrecen, Hungary d Department of Clinical Biochemistry and Molecular Pathology, University of Debrecen, Debrecen, Hungary e Department of Biophysics, University of Pécs, Pécs, Hungary f Laboratorio di Immunologia, Instituto Superiore di Sanita, Rome, Italy |
| 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. |
| Keywords: | P-glycoprotein Multidrug resistance UIC2 Conformation Substrate |
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