Differential effects of estrogen, tamoxifen and the pure antiestrogen ICI 182,780 in human drug-resistant leukemia cell lines

John R. Zalcberg*, Xiu F. Hu, Michael Ching, Alan Wakeling, Dominic M. Wall, Ian C. Marschner, Mario de Luise

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


ICI 182,780, a potent, new steroidal antiestrogen without apparent agonist activity, appears to be a potent modulator of the classic multidrug resistance (MDR) phenotype in the CEM/A7, CEM/VLB100 and K562/VIN100 MDR cell lines. This reagent had no effect on the respective parental CCRF-CEM and K562 cell lines. The use of 1.25 μM ICI 182,780 resulted in a 6- to 7-fold decrease in doxorubicin resistance in the CEM/A7 and CEM/VLB100 cell lines. A dose-response effect was observed at ICI 182,780 concentrations of up to 5 μM. As compared with tamoxifen (TAM), ICI 182,780 was 2 and 4 times more effective in the K562/VIN100 and CEM/A7 cell lines, respectively. ICI 182,780 at 0.625 μM increased [3H]-daunomycin uptake (P<0.0001) as effectively as 5 μM TAM in the resistant CEM/A7 line. Drug-efflux studies showed that 5 μM ICI 182,780 significantly decreased drug efflux as compared with 5 μM TAM (P<0.0001). Estradiol (EST) at 10 μM increased doxorubicin resistance by 1.2-1.3 times in the CEM/A7 and CEM/VLB100 cell lines and significantly decreased drug accumulation (P=0.002) and retention (P<0.001) in the CEM/A7 cell line. However, the addition of 10 μM EST to 1-2 μM ICI 182,780 did not inhibit the ability of ICI 182,780 to modulate doxorubicin resistance in the two resistant cell lines. Using reverse-phase high-performance liquid chromatography (HPLC) to measure lipophilicity, we found no apparent association between the ability of ICI 182,780, TAM or EST to modulate resistance and their relative hydrophobicity.

Original languageEnglish
Pages (from-to)123-129
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Issue number2
Publication statusPublished - Mar 1993
Externally publishedYes


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