Activities of the Microtubule-stabilizing Agents Epothilones A and B with Purified Tubulin and in Cells Resistant to Paclitaxel (Taxol®)

摘要: Epothilones A and B, natural products with minimal structural analogy to taxoids, have effects similar those of paclitaxel (Taxol ® ) in cultured cells on microtubule protein, but differ from retaining activity multidrug-resistant cells. We examined interactions the epothilones purified tubulin additional cell lines, including a paclitaxel-resistant ovarian carcinoma line an altered b-tubulin. The epothilones, like paclitaxel, induced form microtubules at low temperatures without GTP and/or microtubule-associated proteins. are competitive inhibitors binding [ 3 H]paclitaxel polymers. apparent Ki values for B were 1.4 0.7 mM by Hanes analysis 0.6 0.4 Dixon analysis. In paclitaxel-sensitive human lines we examined, epothilone had greater antiproliferative than or while was usually less active paclitaxel. colon retained sensitivity epothilones. With Potorous tridactylis kidney epithelial (PtK2) indirect immunofluorescence, bundles appeared more rapidly following treatment, there different proportions various mitotic aberrations treatment drugs.