Estramustine-induced mitotic arrest in two human prostatic carcinoma cell lines DU 145 and PC-3.
In growth proliferation experiments on two human prostatic carcinoma cell lines, DU 145 cells were found to be more sensitive to the cytotoxic effect of estramustine and nor-nitrogen mustard than PC-3 cells. Estramustine was, however, much more cytotoxic in both cell lines than nor-nitrogen mustard. Cytogenetic experiments revealed that estramustine produced a drastic increase of the mitotic index in both these cell lines. This increase could be accounted for by the arrest of cells in their first treatment-metaphase. The arrested metaphases exhibited all the characteristics commonly found for stathmokinetic agents such as colchicine and vinca-analogues. No mitotic arrest was found for nor-nitrogen mustard but chromosomal aberrations were found at toxic concentrations. Estradiol exhibited minimal toxicity and caused no mitotic arrest in these cell lines. The mitotic arrest induced by estramustine was found to be reversible on removal of the drug.
D002277:Carcinoma / Q000188:drug therapy*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D004961:Estramustine / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D007621:Karyotyping; D008297:Male; D008938:Mitosis / Q000187:drug effects*; D009588:Nitrogen Mustard Compounds / Q000633:toxicity*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D013997:Time Factors
D009588:Nitrogen Mustard Compounds; D004961:Estramustine; C004933:nornitrogen mustard