• Fulltext


        Click here to view fulltext PDF

      Permanent link:

    • Keywords


      Dose– response relationship; drug- membrane interactions; drug synergism; dye leakage; isobole method; multiple drug-resistance

    • Abstract


      Various cationic lipophilic compounds can reverse the multidrug resistance of cancer cells. Possible interaction between these compounds, which are known as modulators, has been assessed by measuring leakage of Sulphan blue from anionic liposomes, induced both by verapamil alone and by verapamil in combination with diltiazem, quinine, thioridazine or clomipramine. An equation was derived to quantify the permeation doses and Hill coefficients of the drugs and mixtures between them by simultaneous fitting of the experimental data. The interaction was tested by two methods, the competition plot and the isobole method; both showed synergy between verapamil and each of diltiazem, quinine and thioridazine. The dose factor of potentiation for verapamil determined within membranes was 4.0 ± 0.4 with diltiazem, 3.2 ± 0.4 with quinine and 2.4 ± 0.3 with thioridazine. The results suggest that the effectiveness of reversing multidrug resistance may be increased with modulators such as verapamil and diltiazem that have a much greater effect in combination than what would be expected from their effects when considered separately.

    • Author Affiliations


      Madeleine Castaing1 2 Alain Loiseau3 Athel Cornish-Bowden4

      1. Faculté de Pharmacie, 27, Boulevard Jean Moulin, 13385 Marseille, France
      2. CNRS Délégation Régionale Languedoc-Roussillon, 34293 Montpellier, France
      3. Faculté de Médecine Xavier -Bichat, 75870 Paris, France
      4. Institut de Biologie Structurale et Microbiologie, 13402 Marseille, France
    • Dates

  • Journal of Biosciences | News

    • Editorial Note on Continuous Article Publication

      Posted on July 25, 2019

      Click here for Editorial Note on CAP Mode

© 2021-2022 Indian Academy of Sciences, Bengaluru.