Abstract

The human mammary cancer cell line MCF-7 in culture was used to study the effect of tamoxifen and its derivatives: 4-hydroxytamoxifen (4-OH-Tam), N-desmethyltamoxifen (Dem-Tam) and cis-tamoxifen (cis-Tam) on the uptake and conversion of [ 3H]estrone sulfate ( 3H-E,S) to estradiol (E 2). When [ 3H]-E 1S (4 × 10 −9 M) was incubated by itself (control) a great proportion of the radioactivity was found as [ 3H]E 2, predominantly in the nuclear fraction. All of the antiestrogens (10 −6 M–10 −5 M) studied decreased the total uptake of radioactivity by the cells by 50–60% and the quantity of E 2 formed. The calculated concentrations (in pg/mg DNA ± S.E.M.) of E 2 (cytosol + 0.6 M KCl nuclear extract) with the anti-estrogens at 10 −5 M were as follows: control 56 ± 3; Tam treated cells 4 ± 1; + 4-OH-Tam 2 ± 1; + Dem-Tam 5 ± 2; + cis-Tam 8 ± 4. A significant decrease in the concentrations of E 2 was also observed in the mitochondria-microsomal fractions after the different treatments. It is suggested that the MCF-7 cells can use estrone-3-sulfate as a source of E 2 and that the inhibitory effect of tamoxifen and its derivatives on the conversion of this sulfate to E 2 could be involved in the anti-estrogenic process of these triphenylethylene derivatives.

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