MONENSIN AND VERAPAMIL DO NOT ALTER INTRACELLULAR-LOCALIZATION OF DAUNORUBICIN IN MULTIDRUG-RESISTANT HUMAN KB CELLS

The effects of monensin, verapamil and several inhibitors of membrane transport processes on the accumulation of [H-3] daunorubicin by human KB-A1 cells have been investigated to determine the role of subcellul ar vesicular transport in the multidrug resistance phenotype. The Golg i inhibitor, brefeldin A, had no effect on drug accumulation, which su ggests that vesicular transport is not a significant factor in drug re sistance in these cells. KB-AI cells were collaterally sensitive to bo th monensin and verapamil. Both of these compounds reduced drug efflux but did not alter subcellular distribution of daunorubicin, consisten t with the view that monensin, like verapamil, acts directly on P-glyc oprotein.