Abstract
Chloride channel currents were measured in drug sensitive parental HL60 and multidrug resistant (MDR) subline HL60 AR cells, using a whole cell patch-clamp technique. In addition, the in vitro effects of 4,4′ diisothiocyana-tostilbene-2,2′-disulfonic acid (DIDS), a Cl- channel blocker, on intracellular accumulation and sensitivity to daunorubicin and intracellular pH (pHi) in HL60 cells were examined. Baseline DIDS blockable Cl- currents were consistently lower in HL60 AR cells (0.9 pA/pF) as compared to HL60 cells (7.0 pA/pF). Similarly cAMP-activated Cl- currents were minimal in HL60 AR cells (0.2 pA/pF) as compared to HL60 cells (8 pA/pF). In vitro treatment of drug sensitive HL60 cells with DIDS resulted in concentration-dependent decreased accumulation and increased resistance to daunorubicin and decreased pHi. These data show that altered Cl- permeability is associated with MDR and suggest that Cl- channels may play a role in MDR.
Original language | English (US) |
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Pages (from-to) | 83-89 |
Number of pages | 7 |
Journal | Cancer Letters |
Volume | 66 |
Issue number | 1 |
DOIs | |
State | Published - Sep 14 1992 |
Keywords
- chloride current
- intracellular pH
- multidrug resistance
ASJC Scopus subject areas
- Oncology
- Cancer Research