D. Yoshida et al., SELECTIVE ANTIMITOTIC EFFECTS OF ESTRAMUSTINE CORRELATE WITH ITS ANTIMICROTUBULE PROPERTIES ON GLIOBLASTOMA AND ASTROCYTES, Neurosurgery, 34(5), 1994, pp. 863-867
ESTRAMUSTINE IS AN estradiol-based agent that accumulates in cells con
taining estramustine binding protein. Previous studies have shown that
this binding site is expressed in human glioblastoma cells and that e
stramustine accumulates in glioma cells, resulting in a concentration-
dependent inhibition of proliferation. We have shown that estramustine
treatment results in a rapid inhibition of deoxyribonucleic acid synt
hesis (within 4 h) in human glioblastoma cells associated with an alte
ration of cell size and shape, consistent with its known antimicrotubu
le activity. To extend these findings, we performed an immunohistochem
ical analysis of microtubules with a monoclonal antibody to beta-tubul
in, using a colorimetric assay with (4,5-dimethylthiazol-2-yl)-2,5-dip
henyltetrazolium bromide to measure the antimitotic effects of estramu
stine on both human glioblastoma and astrocyte cultures. Within 4 hour
s, estramustine (10 mu mol/L) caused a dramatic alteration in the tubu
lin staining in glioma cells, characterized by a disorganization in mi
crotubules. Cell shape and microtubule staining in astrocytes were rel
atively preserved. Estramustine had a concentration-dependent cytotoxi
c effect in tumor cultures, whereas it had no effect on astrocyte viab
ility at any concentration. Differences in the antimitotic effects do
not appear to be related to variations in proliferation rates among th
ese different types of cells. These data suggest that although estramu
stine is a potent inhibitor of proliferation in glioblastoma cells, it
has modest antiproliferative effects on astrocytes and its selective
activity is closely correlated with its antimicrotubule properties.