Reversal of resistance to rhodamine 123 in adriamycin-resistant Friend leukemia cells.
Pleiotropic resistance to rhodamine 123 (Rho-123) in Adriamycin (ADM)-resistant Friend leukemia cells was circumvented by cotreatment with 10 microM verapamil. Increased cytotoxicity corresponded to higher intracellular Rho-123 levels. The verapamil-induced increase of drug accumulation in resistant cells is accounted for at least in part by the blockage or slowing of Rho-123 efflux from these cells. In contrast, accumulation and consequent cytotoxicity of Rho-123 in sensitive cells are not increased by verapamil. Similar results were obtained when ADM was used in this cell system. These results suggest that the efflux system for Rho-123 and ADM in sensitive cells is either reduced or absent. Although Rho-123 accumulates specifically in mitochondria and ADM mainly in the nucleus, the loss of these two different classes of compounds from resistant cells appears to occur via a similar or common mechanism. The similarities in drug transport between Rho-123 and ADM may have important implications when applied to an in vivo environment.
D000818:Animals; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology*; D004351:Drug Resistance; D005622:Friend murine leukemia virus; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000473:pathology*; D020112:Rhodamine 123; D012235:Rhodamines / Q000378:metabolism / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology; D014966:Xanthenes / Q000494:pharmacology*
D012235:Rhodamines; D014966:Xanthenes; D020112:Rhodamine 123; D004317:Doxorubicin; D014700:Verapamil