Interaction of Rhizoxin with Bovine Brain Tubulin

Angelique S. Sullivan, Veena Prasad, Mary Carmen Roach, Richard F. Ludueňa, Masaaki Takahashi, Shigeo Iwasaki

Producción científica: Articlerevisión exhaustiva

53 Citas (Scopus)

Resumen

Rhizoxin is an antitumor drug prepared from the fungus Rhizopus chinensis. It is an inhibitor of microtubule assembly and a potent competitive inhibitor of the binding of tubulin of ansamitocin P-3, a maytan-sine analogue. Rhizoxin also weakly inhibits vinblastine binding to tubulin. We have previously found that maytansine and vinblastine differ strikingly from each other in many ways, including their effects on tubulin sulfhydryl groups and on tubulin decay. Since the structure of rhizoxin is very different from that of vinblastine and only slightly resembles that of maytansine, we decided to compare its interaction with tubulin with those of the other two drugs, using systems which discriminate between the effects of the latter two drugs. We found that rhizoxin acts like maytansine in that it completely prevents formation of an intrachain cross-link in ²-tubulin by N,N’-ethylenebis(iodoacetamide), whereas vinblastine only partially inhibits this. Half-maximal inhibition of formation of this cross-link was observed at 2.5 µm rhizoxin. We found previously that the rate of binding of tubulin to the fluorescent probe bis(8-anilino-naphthalene 1-sulfonate) is a good indicator of tubulin decay and that vinblastine strongly inhibits this, whereas maytansine has no effect. We here report that rhizoxin acts like maytansine in that it has no effect on decay. Thus, despite the fact that its resemblance to maytansine is small, rhizoxin appears to interact with tubulin in very much the same way as does maytansine.

Idioma originalEnglish (US)
Páginas (desde-hasta)4277-4280
Número de páginas4
PublicaciónCancer Research
Volumen50
N.º14
EstadoPublished - jul 15 1990

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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