Antimicrotubule effects of estramustine, an antiprostatic tumor drug.
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. We have studied the cytotoxic effects of EM on the cytoskeletal organization of squirrelfish pigment cells (erythrophores) and human prostatic tumor cells (DU 145) in culture. Light and whole-mount electron microscopy studies reveal that, at microM levels (60 to 120 microM), 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 145s. 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.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D002460:Cell Line; D004961:Estramustine / Q000494:pharmacology*; D005399:Fishes; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000187:drug effects*; D008938:Mitosis / Q000187:drug effects; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology*; D010860:Pigments, Biological / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000648:ultrastructure
D009588:Nitrogen Mustard Compounds; D010860:Pigments, Biological; D004961:Estramustine; D002118:Calcium