Uptake, metabolism and antiproliferative effect of estramustine phosphate in human glioma cell lines

The uptake, metabolism and antiproliferative effects of estramustine phosphate, a cytotoxic agent used in prostatic cancer, were investigated in the two human malignant glioma cell lines U-105 MG and U-251 MG. The primary metabolite estramustine had a dose-dependent inhibitory effect on cell proliferation within the concentration range 5-20 micrograms/ml. After incubation with 3H-estramustine phosphate in both cell lines, a progressive uptake of radioactivity was recorded during 24 hours. A significant metabolism of parent estramustine phosphate into estramustine and estramustine, which is a well known part of the metabolic pathway in man, was also demonstrated. In conclusion, certain cultured malignant glioma cells display significant uptake, retention and metabolism of estramustine phosphate and further studies are indicated to assess the clinical implications of these findings.