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  • Title: Selective antimitotic effects of estramustine correlate with its antimicrotubule properties on glioblastoma and astrocytes.
    Author: Yoshida D, Cornell-Bell A, Piepmeier JM.
    Journal: Neurosurgery; 1994 May; 34(5):863-7; discussion 867-8. PubMed ID: 8052384.
    Abstract:
    Estramustine is an estradiol-based agent that accumulates in cells containing estramustine binding protein. Previous studies have shown that this binding site is expressed in human glioblastoma cells and that estramustine 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 synthesis (within 4 h) in human glioblastoma cells associated with an alteration of cell size and shape, consistent with its known antimicrotubule activity. To extend these findings, we performed an immunohistochemical analysis of microtubules with a monoclonal antibody to beta-tubulin, using a colorimetric assay with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide to measure the antimitotic effects of estramustine on both human glioblastoma and astrocyte cultures. Within 4 hours, estramustine (10 mumol/L) caused a dramatic alteration in the tubulin staining in glioma cells, characterized by a disorganization in microtubules. Cell shape and microtubule staining in astrocytes were relatively preserved. Estramustine had a concentration-dependent cytotoxic effect in tumor cultures, whereas it had no effect on astrocyte viability at any concentration. Differences in the antimitotic effects do not appear to be related to variations in proliferation rates among these different types of cells. These data suggest that although estramustine 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.
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