ANTIMICROTUBULE EFFECTS OF ESTRAMUSTINE, AN ANTIPROSTATIC TUMOR DRUG

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (8) , 3891-3897
Abstract
Estramustine [17.beta.-estradiol 3 N bis(2-chloroethyl)carbamate; EM] is a stable conjugate of estradiol and nor-nitrogen mustard that is used for the treatment of human prostatic carcinoma. The cytotoxic effects were studied of EM on the cytoskeletal organization of squirrelfish [Holocentrus ascensionis] pigment cells (erythrophores) and human prostatic tumor cells (DU 145) in culture. Light and whole-mount EM studies reveal that, at .mu.M levels (60-120 .mu.M), EM has a dose-dependent disruptive effect on cell shape, cytoskeletal organization and intracellular transport. Upon removal of the drug, the cytological effects of EM are rapidly reversible in fish cells but not DU 145. Immunofluorescent studies reveal that EM produces microtubule disassembly in fish erythrophores and DU 145 cells. A concomitant disruption of actin-microfilament arrays also occurs in DU 145 cells. These morphological data suggest that EM, in contradistinction to its constituent estradiol:nitrogen mustard species, induces cytotoxicity as an antimicrotubule drug. The observed disruption of the microtubules and cytomatrix of interphase cells is not reversible in the prostatic carcinoma cells. The disruptive action of EM on the cytoskeleton could ultimately produce a cytotoxic antimitotic effect in dividing cells.