Reversal of Resistance to Rhodamine 123 in Adriamycin-resistant Friend Leukemia Cells

Theodore J. Lampidis, Jean Nicolas Munck, Awtar Krishan, Haim Tapiero

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Abstract

Pleiotropic resistance to rhodamine 123 (Rho-123) in Adriamycin (ADM)-resistant Friend leukemia cells was circumvented by cotreatment with 10 μM 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.

Original languageEnglish (US)
Pages (from-to)2626-2631
Number of pages6
JournalCancer Research
Volume45
Issue number6
StatePublished - Jun 1 1985

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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