EFFECT OF ESTRAMUSTINE PHOSPHATE ON THE ASSEMBLY OF ISOLATED BOVINE BRAIN MICROTUBULES AND FAST AXONAL-TRANSPORT IN THE FROG SCIATIC-NERVE

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (5) , 2234-2239
Abstract
Estramustine phosphate (0.01-0.5 mM), an estradiol mustard derivative used in the therapy of prostatic carcinoma, inhibited the assembly of brain microtubule proteins in vitro and disassembled preformed microtubules. In the presence of estramustine phosphate, the minimum microtubule-protein concentration sufficient for the assembly of microtubules was increased. Low concentrations of taxol (20 .mu.M) completely reversed the inhibition of assembly by estramustine phosphate. The effects were specific to estramustine phosphate since neither estradiol 17.beta.-phosphate, the hormonal moiety of the drug, nor nomitrogen mustard, the alkylating moiety, had any effect on assembly. Estramustine phosphate (0.1-0.5 mM) was also found to reversibly inhibit fast axonal transport in the frog sciatic nerve. The nerve content of ATP, ADP and AMP was not significantly affected by estramustine phosphate. The cytotoxic action of estramustine phosphate could be dependent partially on an interaction with microtubules, probably via the microtubule-associated proteins.