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Reversal of Acquired Resistance to Doxorubicin in P388 Murine Leukemia Cells by Tamoxifen and Other Triparanol Analogues¹

Department of Radiation and Clinical Oncology, Hadassah University Hospital, P. O. Box 12000, Jerusalem, Israel 91120 [A. R., Z. F], and The Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland 20205 [D. G.]

The effects of the triparanol analogues chlorotrianisene, clomiphene, tamoxifen, 5-[p-(fluoren-9-ylidenemethyl)phenyl]-2-piperidineethanol (MDL 10393), MDL 8917v, nafoxidine, 2-[p-(6-methoxy-2-phenylinden-3-yl)phenoxy]triethylamine (U-11555A), 2-[p-(3,4-dihydro-6-methoxy-2-phenyl-1-naphthyl)phenoxy]triethylamine (U-10520A), and nitromifene, as well as triparanol itself, were studied in the P388 murine leukemia cell line and in a doxorubicin-resistant subline (P388/ADR). At noninhibitory concentrations, all the analogues increased the sensitivity of P388/ADR cells to doxorubicin but did not have such an effect on the doxorubicin-sensitive cells.

Diethylstillbestrol, deacetylated cyclofenil (F6060), hexestrol, and 17ß-estradiol did not have such an activity. The effects of tamoxifen on doxorubicin sensitivity of P388/ADR cells could not be reversed by 17ß-estradiol. Estrogen receptors could not be demonstrated in either cell line. It is therefore suggested that the reversal of the doxorubicin-acquired resistance by the triparanol analogues is unrelated to their estrogenic or antiestrogenic activities. The possible clinical implications of these findings are discussed.

¹ This work was supported by grant from the Israel Cancer Research Fund.

² To whom requests for reprints should be addressed.

Received 1/20/84. Accepted 5/31/84.

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