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Abnormal chloride conductance in multidrug resistant HL60/AR cells
S Gollapudi1, T McDonald, P Gardner
1Division of Basic and Clinical Immunology, University of California, Irvine 92717.
Cancer Letters
|September 14, 1992
Summary
Multidrug resistance (MDR) in cancer cells is linked to altered chloride channel activity. Blocking these channels with DIDS affects drug accumulation and pH, suggesting a role for chloride channels in MDR.
Area of Science:
- Cellular Biology
- Pharmacology
- Oncology
Background:
- Multidrug resistance (MDR) is a major challenge in cancer chemotherapy.
- Chloride channels play roles in various cellular processes, including pH regulation and ion transport.
Purpose of the Study:
- To investigate the role of chloride channels in multidrug resistance (MDR) in HL60 leukemia cells.
- To examine the effects of a chloride channel blocker, DIDS, on drug accumulation, sensitivity, and intracellular pH.
Main Methods:
- Whole cell patch-clamp technique to measure chloride channel currents.
- In vitro experiments using HL60 and HL60/AR (MDR subline) cells.
- Treatment with 4,4' diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and daunorubicin.
Main Results:
- Baseline and cAMP-activated chloride currents were significantly lower in MDR HL60/AR cells compared to sensitive HL60 cells.
- DIDS treatment in HL60 cells led to decreased daunorubicin accumulation and increased resistance.
- DIDS also caused a concentration-dependent decrease in intracellular pH (pH(i)) in HL60 cells.
Conclusions:
- Altered chloride permeability is associated with multidrug resistance in HL60 cells.
- Chloride channels may represent a therapeutic target for overcoming MDR in cancer.