Inhibition of estrogen synthesis in human breast tumors by testololactone and bromoandrostenedione.
The inhibition of aromatase enzyme in human breast tumors by delta 1-testololactone, testololactone, 6 alpha-bromoandrostenedione, and 6 beta-bromoandrostenedione was investigated. Estrone and estradiol synthesis from androstenedione was reduced in 3 tumor incubations by the presence of 0.13 mM delta 1-testololactone and testololactone. 6 alpha- and 6 beta-bromoandrostenedione (2.0 microM) were also shown to block estrogen synthesis in 2 tumors. Furthermore, Lineweaver-Burk plots revealed that all 4 compounds are competitive inhibitors of androstenedione aromatization. An apparent Km of the aromatase enzyme for androstenedione of 0.08 microM and a Vmax of 23 pmol of estrone synthesized/g tumor/hr were determined for one human breast tumor specimen. These results demonstrate that these aromatase inhibitors may be useful for the treatment of breast cancer.
D000735:Androstenedione / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000378:metabolism*; D004958:Estradiol / Q000096:biosynthesis*; D004970:Estrone / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007700:Kinetics; D013260:Steroids, Heterocyclic / Q000494:pharmacology*; D013738:Testolactone / Q000031:analogs & derivatives*
D047072:Aromatase Inhibitors; D013260:Steroids, Heterocyclic; D004970:Estrone; C025177:6-bromoandrostenedione; C018155:testololactone; D000735:Androstenedione; D004958:Estradiol; D013738:Testolactone