Reversal of acquired resistance to doxorubicin in P388 murine leukemia cells by tamoxifen and other triparanol analogues.

Abstract:

: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. Diethylstilbestrol, deacetylated cyclofenil (F6060), hexestrol, and 17 beta-estradiol did not have such an activity. The effects of tamoxifen on doxorubicin sensitivity of P388/ADR cells could not be reversed by 17 beta-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.

journal_name

Cancer Res

journal_title

Cancer research

authors

Ramu A,Glaubiger D,Fuks Z

subject

Has Abstract

pub_date

1984-10-01 00:00:00

pages

4392-5

issue

10

eissn

0008-5472

issn

1538-7445

journal_volume

44

pub_type

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