INHIBITION OF MICROTUBULE ASSEMBLY IS A POSSIBLE MECHANISM OF ACTION OF MITOXANTRONE

We have found that mitoxantrone can inhibit the polymerization of brain tubulinin a dose dependent manner. MXT had relatively high affinity for tubulin but had no appreciable effect on tubulin associated guanosinetriphosphatase (GTPase) activity nor could it compete with vinblastine(VB) and colchicine (Col) for tubulin binding sites. Furthermore, MXT (0.1-10 μ M) is antiproliferative to cold-treated (0°C) epithelial cells afteronly brief exposure (30 min). These results indicated that MXTis amicrotubule inhibitory agent and can exert its anticellular effect through modulation of microtubule assembly. © 1991 Academic Press, Inc.