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Related Experiment Videos

Membrane potential differences between adriamycin-sensitive and -resistant cells as measured by flow cytometry.

M Hasmann1, G K Valet, H Tapiero

  • 1Max-Planck Institut fur Biochemie, Mildred-Scheel-Labor fur Krebszellforschung, Martinsried, F.R.G.

Biochemical Pharmacology
|January 15, 1989
PubMed
Summary

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Drug resistance in leukemia cells is linked to altered cell membrane potential. Verapamil affects drug uptake differently in sensitive and resistant cells, suggesting new therapeutic strategies for multiple drug resistance.

Area of Science:

  • Cell Biology
  • Pharmacology
  • Cancer Research

Background:

  • Adriamycin (ADM)-resistant Friend leukemia cells (FLC) exhibit altered drug uptake compared to sensitive cells.
  • Plasma membrane potential differences may influence the accumulation and efficacy of positively-charged chemotherapeutic agents in multidrug-resistant (MDR) cancer cells.

Purpose of the Study:

  • To investigate the role of plasma membrane potential in ADM-sensitive and ADM-resistant FLC.
  • To evaluate the effect of verapamil, a calcium channel antagonist, on the accumulation of fluorescent probes in sensitive and MDR FLC.

Main Methods:

  • Utilized the fluorescent membrane potential probe 3,3'-dihexyl-oxacarbocyanine (DiOC6(3)) to measure membrane potential.
  • Assessed DiOC6(3) uptake in the presence of high potassium (K+) and carbonylcyanide 4-trifluoromethoxy-phenylhydrazone (FCCP).

Related Experiment Videos

  • Investigated the impact of verapamil on the accumulation of DiOC6(3), Rhodamine 123 (Rho 123), and INDO-1/AM in sensitive and MDR FLC.

    • Main Results:

    • ADM-sensitive FLC showed a 4-fold higher DiOC6(3) uptake than resistant cells, indicating a greater plasma transmembrane potential.
    • Verapamil increased DiOC6(3) accumulation in both sensitive (1.5-fold) and MDR FLC (1.9-fold), suggesting it enhances membrane potential.
    • Verapamil significantly increased Rho 123 accumulation in MDR FLC (7.8-fold) by likely inhibiting the MDR efflux pump, while decreasing it in sensitive cells.

    Conclusions:

    • Differences in plasma membrane potential contribute to drug resistance in FLC.
    • Verapamil influences drug accumulation through mechanisms involving both plasma membrane potential modulation and inhibition of MDR efflux pumps.
    • Verapamil demonstrates a novel effect on drug accumulation in MDR cells, warranting further investigation into its therapeutic potential.