Phenylazoxycyanide damages microtubular protein more than its reference antibiotic, calvatic acid

Abstract

The effect of phenylazoxycyanide and calvatic acid, its reference antibiotic, on some functions of tubulin obtained from different sources has been studied. Our purpose was to establish a possible correlation between the antitumour activity of these drugs and their antimicrotubular action. Microtubules are subcellular structures involved in proliferation and maintenance of the cell shape and probably in malignant transformation; indeed most antimitotic drugs influence the stability of microtubules through the interaction with tubulin, their main protein. In this work we found phenylazoxycyanide impairs, more than calvatic acid, polymerization of purified tubulin from calf brain. It also damages, in a dose-dependent manner, colchicine-binding ability of tubulin derived from rat liver and AH-130 Yoshida ascite hepatoma cells. Compounds displaying an azoxycyano group may represent new antimicrotubular agents and their effect could be modulated by the different polarity and structural characteristic of the molecule.