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 language | English |
|---|---|
| Pages (from-to) | 2626-2631 |
| Number of pages | 6 |
| Journal | Cancer Research |
| Volume | 45 |
| Issue number | 6 |
| State | Published - Jan 1 1985 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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Reversal of resistance to rhodamine 123 in adriamycin-resistant Friend leukemia cells. / Lampidis, Theodore; Munck, J. N.; Krishan, A.; Tapiero, H.
In: Cancer Research, Vol. 45, No. 6, 01.01.1985, p. 2626-2631.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Reversal of resistance to rhodamine 123 in adriamycin-resistant Friend leukemia cells
AU - Lampidis, Theodore
AU - Munck, J. N.
AU - Krishan, A.
AU - Tapiero, H.
PY - 1985/1/1
Y1 - 1985/1/1
N2 - 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.
AB - 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.
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M3 - Article
VL - 45
SP - 2626
EP - 2631
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 6
ER -