Frog Sciatic Nerve Bovine Brain Microtubules and Fast Axonal Transport in the Effect of Estramustine Phosphate on the Assembly of Isolated

MATERIALS AND METHODS Estramustine phosphate (0.01 to 0.5 HIM),an estradici mustard derivative used in the therapy of prostatic carcinoma, inhibited the assembly of brain microtubule proteins in vitro and disassem bled preformed microtubules. In the presence of estramustine phosphate, the minimum microtubule-protein concentration suf ficient for the assembly of microtubules was increased. Low concentrations of taxol (20 U.M)completely reversed the inhibition of assembly by estramustine phosphate. The effects were spe cific to estramustine phosphate since neither estradiol 170phosphate, the hormonal moiety of the drug, nor nornitrogen mustard, the alkylating moiety, had any effect on assembly. Estramustine phosphate (0.1 to 0.5 HIM) was also found to reversibly inhibit fast axonal transport in the frog sciatic nerve. The nerve content of adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate was not significantly af fected by estramustine phosphate. Our results suggest that the cytotoxic action of estramustine phosphate could be dependent partially on an interaction with microtubules, probably via the microtubule-associated proteins.