Immunofluorescent studies of the anti-microtubule effects of the anti-cancer drug estramustine.
Immunofluorescent studies in human prostatic carcinoma cells (DU 145) and cultured squirrel fish epithelial cells (a non-cancer cell) revealed that estramustine, a conjugate of estradiol and nor-nitrogen mustard, possessed microtubule disassembly properties. Sixty microM estramustine produced disassembly at both the proximal and distal ends of microtubules, producing short pieces of less than 2 microM which were "wavy" and oriented in a random manner. With increased time of drug exposure these short microtubules disappeared, to be accompanied by a gradual disassembly of a small population of longer microtubules (greater than 7-8 microM). In dividing DU 145 cells it was possible to show a different degree of sensitivity of specific microtubule-containing cellular structures. In mitotic figures the asters were most sensitive and disappeared completely following exposure to estramustine. These were followed by the "pole-to-pole" and "chromosomal" fibers. In cytokinesis, the intercellular fibers between daughter cells were comparatively resistant to the drug. Estramustine did not induce disassembly of the vimentin filaments in non-dividing or dividing cells but did cause their collapse around the nucleus or the mitotic apparatus. These data suggest that specific microtubules have differing sensitivity to estramustine.
Wang
M
M
Department of Pharmacology, Fox Chase Cancer Center, Philadelphia, PA 19111.
Tew
K D
KD
Stearns
M E
ME
D002478:Cells, Cultured; D004848:Epithelium / Q000187:drug effects; D004961:Estramustine / Q000627:therapeutic use*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007399:Interphase; D008297:Male; D008870:Microtubules / Q000187:drug effects*; D009588:Nitrogen Mustard Compounds / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014746:Vimentin / Q000032:analysis
D009588:Nitrogen Mustard Compounds; D014746:Vimentin; D004961:Estramustine