Studies on the mammary tumor-inhibiting effects of diethylstilbestrol and its mono- and diphosphate.
Diethylstilbestrol (DES), diethylstilbestrol monophosphate (DES-MP) and diethylstilbestrol diphosphate (DES-DP) were tested for their estrogen receptor affinity, estrogenic potency and mammary tumor-inhibiting activity in vitro and in vivo. DES had a much higher receptor binding affinity than its mono- or diphosphate. All three compounds inhibited the growth of the hormone-dependent MCF-7 and hormone-independent MDA-MB 231 breast cancer line only at relatively high concentrations. The estrogenic potency in the immature mouse uterine weight test decreased in the order DES greater than DES-MP much greater than DES-DP. The hormone-dependent MXT mammary tumor of the mouse was inhibited by all three compounds at a dosage of 1.0 mg/kg per week. At a dose of 0.01 mg/kg, DES, DES-MP, and DES-DP stimulated the tumor growth. Thus, for the first time, a biphasic effect on tumor growth was demonstrated in intact mature animals. As the effects of all three compounds were similar in this assay, a cleavage of the phosphate groups is likely. A decrease in estrogenic potency concomitant with a retained antitumor effect of DES-MP and DES-DP compared to DES was not demonstrable in the mature mouse using the MXT assay, only in the uterotrophic test in the immature mouse.
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy; D002460:Cell Line; D004054:Diethylstilbestrol / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D011959:Receptors, Estradiol / Q000187:drug effects; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
D011959:Receptors, Estradiol; C048587:diethylstilbestrol monophosphate; D004958:Estradiol; D004054:Diethylstilbestrol; C004955:fosfestrol