7α-(4′-Amino)phenylthio-1,4-androstadiene-3,17-dione (7α-APTADD), a potent enzyme-activated irreversible inhibitor, was examined in two different human cell culture lines, MCF-7 human mammary carcinoma cells and JAr choriocarcinoma cells. Both the MCF-7 and JAr cell culture systems exhibit aromatase activity, and 7α-APTADD was evaluated for its aromatase-inhibitory activity, for its ability to inactivate the enzyme complex, and for the time course of recovery of enzymatic activity. This inhibitor produced a dose-dependent inhibition of aromatase activity in MCF-7 cells and in JAr cells, with EC50 values of 91 and 7.3 nm, respectively. Two other steroidal inhibitors, 7α-(4′-amino)phenylthio-4-androstene-3,17-dione and 4-hydroxyandrostenedione, produced similar dose-response curves and EC50 values, while the nonsteroidal aminoglutethimide was less effective. Both cell culture systems exhibited prolonged inhibition of aromatase activity following exposure to 7α-APTADD, suggesting enzyme inactivation by this inhibitor. Thus, 7α-APTADD is an effective inhibitor of aromatase in MCF-7 mammary carcinoma cells and in JAr choriocarcinoma cells. These studies encourage further development of this group of medicinal agents for the treatment of estrogen-dependent mammary carcinoma.

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Portions of this work were presented at the Annual Meeting of the American Association of Cancer Research, San Francisco, CA, May 24–27, 1989, and at the 70th Annual Meeting of the Endocrine Society, New Orleans, LA, June 8–10, 1988. This work was supported by American Cancer Society Grant BC-482 and NIH Grant P30-CA16058.

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