SELECTIVE ANTIMITOTIC EFFECTS OF ESTRAMUSTINE CORRELATE WITH ITS ANTIMICROTUBULE PROPERTIES ON GLIOBLASTOMA AND ASTROCYTES

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.