Effects of the aromatase inhibitor 7 alpha-(4'-amino)phenylthio-4-androstene-3,17-dione in MCF-7 human mammary carcinoma cell culture.
7 alpha-Substituted 4-androstene-3,17-diones are effective inhibitors of aromatase in vitro. The microsomal P-450 enzyme complex has a greater affinity for several of these inhibitors than for the substrate androstenedione, with 7 alpha-(4'-amino)phenylthio-4-androstene-3,17-dione (7 alpha-APTA) being the most potent competitive inhibitor of the series. The effects of 7 alpha-APTA were examined in MCF-7 human mammary carcinoma cell culture. 7 alpha-APTA inhibited aromatase activity in the MCF-7 human mammary carcinoma cell line with an ED50 value of 25.07 nM (+/- 7.71). The inhibitor did not bind to the estrogen receptor of the MCF-7 cells in vitro. In addition, 7 alpha-APTA did not stimulate growth of the MCF-7 cells when compared with controls. No induction of progesterone receptors was observed in MCF-7 cultures grown in the presence of inhibitor at concentrations ranging from 10 pM to 1 microM. Thus, the steroid 7 alpha-APTA is an effective inhibitor of aromatase in intact MCF-7 cells. Furthermore, it does not demonstrate any significant hormonal effects on the cells nor does this agent produce any general toxicological effects.
D000735:Androstenedione / Q000031:analogs & derivatives* / Q000494:pharmacology; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000096:biosynthesis
D047072:Aromatase Inhibitors; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000735:Androstenedione; C028626:7-(4'-amino)phenylthioandrostenedione