EVIDENCE FOR A NON-ESTROGENIC CYTOSTATIC EFFECT OF ESTRAMUSTINE ON HUMAN PROSTATIC-CARCINOMA CELLS INVIVO

Estramustine is one of the main metabolites of estramustine phosphate (Estracyt(R)), a drug used in the treatment of advanced prostatic cancer. In the present study the hormone independent human prostatic carcinoma cell line DU 145 implanted subcutaneously in nude mice (NMRI) was used to investigate the mode of action of estramustine in vivo. Metaphase arrest was found in mice treated with estramustine intraperitoneally, 200 and 400-mu-g daily for 2 weeks, 5 days a week. A significant dose dependent decrease in the number of anaphase figures was found. A 7 to 8 fold increase in the number of abnormal metaphases, i.e., highly contracted and unaligned chromosomes, was found. Uptake and retention of H-3-estramustine was found in tumour tissue. No increase in the mitotic index or the number of abnormal metaphases was found in animals treated with polyestradiol phosphate (Estradurin(R)). This is the first time evidence has been presented demonstrating the anti-mitotic effect of estramustine in vivo.