Action of danazol on the conversion of estrone sulfate to estradiol and on the sulfatase activity in the MCF-7, T-47D and MDA-MB-231 human mammary cancer cells

B.‐L. Nguyen, I Fermé, Gérard S. Chetrite, Jörge R. Pasqualini
In: The Journal of Steroid Biochemistry and Molecular Biology · 1993 · vol. 46(1) , pp. 17–23 · doi:10.1016/0960-0760(93)90204-a · PMID:8338787 · W1977746635
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Danazol inhibited the conversion of estrone sulfate to estradiol and sulfatase activity in three human mammary cancer cell lines: MCF-7, T-47D, and MDA-MB-231.

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Abstract

In the present studies the action of Danazol on the conversion of estrone sulfate (E1S) to estradiol (E2) as well as on the sulfatase activity in the MCF-7 and T-47D, hormone-dependent, and MDA-MB-231, hormone-independent, mammary cancer cell lines was explored. Using intact cells we observed that Danazol blocks very significantly the radioactivity uptake and the conversion of [3H]E1S to E2 in all the cells studied. In particular, a very strong effect (85% decrease of these parameters versus the control values) is observed in the T-47D cells. In another series of studies using cell homogenates it is observed that Danazol inhibits the sulfatase activity in all these cell lines. The effect of Danazol is dose-dependent and significant from a concentration of 1 microM. At concentrations of 8 microM E1S, 10(-5) M Danazol, the inhibition of sulfatase activity is 38% in MCF-7, 36% in MDA-MB-231, and 27% in T-47D cells. Analysis by Lineweaver-Burk plot shows that the inhibitory effect is competitive. As E1S is one of the main sources of E2 in human mammary tumors, the present data could open new possibilities for therapeutic applications in hormone-dependent breast cancer.

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