Microtubule depolymerization in Uromyces appendiculatus by three new antineoplastic drugs: combretastatin A-4, dolastatin 10 and halichondrin B

Abstract

Three new antineoplastic natural products, combretastatin A-4, dolastatin 10 and halichondrin B, have been evaluated for their antimicrotubule activity in Uromyces appendiculatus urediniospore germlings using indirect immunofluorescence microscopy. In control germlings microtubules were abundant and mostly oriented parallel to the longitudinal axis of the cell. The microtubule cytoskeleton of germlings treated with 1·3×10⁻⁵M (10 μg ml⁻¹) dolastatin 10 and 4·5×10⁻⁵M (50 μg ml⁻¹) halichondrin B disrupted the microtubule cytoskeleton resulting in the near elimination of microtubule-associated fluorescence. Combretastatin A-4 was less effective, requiring a concentration of 3·2×10⁻³M (1·0 mg ml⁻¹) to disrupt the microtubule cytoskeleton. These effective doses are consistent with previously examined antimicrotubule agents (e.g. nocodazole, griseofulvin, vincristine sulphate, demecolcine).