The effect of the aromatase inhibitor, 4-(phenylthio)-4-androstene-3,17-dione, on dimethylbenz(A)anthracene-induced rat mammary tumors.
4-(Phenylthio)-4-androstene-3,17-dione (4-PTAD), a known inhibitor of human placental aromatase, was examined as a growth inhibitor of DMBA-induced rat mammary tumors. Subcutaneous administration of 4-PTAD at dose levels of 25 or 50 mg/kg/day caused a significant decrease in hormone-dependent tumor growth. Resumption of tumor growth occurred when either the administration of inhibitor was stopped or when inhibitor was coadministered with estradiol indicating that suppression of tumor growth was due to inhibition of estrogen biosynthesis. Additionally, plasma levels of estradiol were found to be lower in the animals treated with 4-PTAD. The major metabolite of 4-PTAD in vitro was identified as 4-(phenylthio)-4-androstene-17 beta-ol-3-one and was found to have 60% of the aromatase inhibitory activity of 4-PTAD.
Abul-Hajj
Y J
YJ
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis 55455.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; C063185:4-(phenylthio)-4-androstene-3,17,dione; D000735:Androstenedione; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene