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Activities of the microtubule-stabilizing agents epothilones A and B with purified tubulin and in cells resistant to paclitaxel (Taxol(R)).
| Content Provider | Semantic Scholar |
|---|---|
| Author | Kowalski, Ryan Giannakakou, Paraskevi Hamel, Ernest |
| Copyright Year | 1997 |
| Abstract | Epothilones A and B, natural products with minimal structural analogy to taxoids, have effects similar to those of paclitaxel (Taxol(R)) in cultured cells and on microtubule protein, but differ from paclitaxel in retaining activity in multidrug-resistant cells. We examined interactions of the epothilones with purified tubulin and additional cell lines, including a paclitaxel-resistant ovarian carcinoma line with an altered beta-tubulin. The epothilones, like paclitaxel, induced tubulin to form microtubules at low temperatures and without GTP and/or microtubule-associated proteins. The epothilones are competitive inhibitors of the binding of [3H]paclitaxel to tubulin polymers. The apparent Ki values for epothilones A and B were 1.4 and 0.7 microM by Hanes analysis and 0.6 and 0.4 microM by Dixon analysis. In the paclitaxel-sensitive human cell lines we examined, epothilone B had greater antiproliferative activity than epothilone A or paclitaxel, while epothilone A was usually less active than paclitaxel. A multidrug-resistant colon carcinoma line and the paclitaxel-resistant ovarian line retained sensitivity to the epothilones. With Potorous tridactylis kidney epithelial (PtK2) cells examined by indirect immunofluorescence, microtubule bundles appeared more rapidly following epothilone B treatment, and there were different proportions of various mitotic aberrations following treatment with different drugs. |
| Starting Page | 153 |
| Ending Page | 156 |
| Page Count | 4 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.cornellpharmacology.org/faculty/labs/giannakakou/documents/KowalskiRJetal.JBiolChem.1997.pdf |
| PubMed reference number | 8999970v1 |
| Volume Number | 272 |
| Issue Number | 4 |
| Journal | The Journal of biological chemistry |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Cold Temperature Colon Carcinoma Cultured Cell Line Epithelial ovarian cancer Epothilones Genus Potorous Guanosine Triphosphate Microtubules Natural Products Paclitaxel Renal Tissue Taxoids epothilone A epothilone B ixabepilone |
| Content Type | Text |
| Resource Type | Article |
