Effect of diethylstilbestrol on the polymerization and alkylation of tubulin

Veena Prasad, Stuart E. Garber, Richard F. Ludueña

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Diethylstilbestrol is a drug used to treat prostate cancer. It is thought to bind to tubulin, the subunit protein of microtubules, at the colchicine-binding site. We examined its interaction with tubulin in more detail. Diethylstilbestrol inhibits microtubule assembly, and seems to do so more effectively when tubulin polymerization is catalyzed by MAP2 rather than tau. Diethylstilbestrol also inhibits the intrachain cross-linking of tubulin by N,N'-ethylenebis-(iodoacetamide) in a pattern similar to that shown by colchicine and the drugs which bind to tubulin at the colchicine-binding site. Unlike most of this category of drugs, however, diethylstilbestrol accelerates, rather than inhibits, the decay of tubulin as measured by exposure of sulfhydryl groups and hydrophobic areas. It appears, therefore, that diethylstilbestrol interacts with tubulin in a manner similar to that of the analogs of the A-ring of colchicine, whose effect on tubulin cross- linking is similar to that of diethylstilbestrol and which also enhance tubulin decay.

Original languageEnglish (US)
Pages (from-to)104-112
Number of pages9
JournalDrug Development Research
Volume48
Issue number3
DOIs
StatePublished - Dec 1 1999

Keywords

  • Antitumor drugs
  • Diethylstilbestrol
  • Microtubules
  • Tubulin

ASJC Scopus subject areas

  • Drug Discovery

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