Epothilone A induces apoptosis in neuroblastoma cells with multiple mechanisms of drug resistance |
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Authors: | Wolff A Technau A Brandner G |
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Affiliation: | UNIV FREIBURG,ABT VIROL,INST MED MIKROBIOL & HYG,D-79008 FREIBURG,GERMANY. UNIV FREIBURG,FAK BIOL,D-79008 FREIBURG,GERMANY. |
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Abstract: | Epothilone A, a novel macrolide antibiotic, is produced by the myxobacterium Sorangium cellulosum. Similarly to paclitaxel (Taxol), epothilone A inhibits cell proliferation and induces apoptosis by binding to tubulin and stabilizing of microtubuli. Like paclitaxel, epothilone A induced apoptosis in neuroblastoma cells which exhibit constitutive cytoplasmic sequestration of p53 and, hence, an impaired DNA-damage-dependent apoptosis. However, in contrast to paclitaxel, epothilone A was also effective against a constitutively Pgp-expressing, multidrug resistant neuroblastoma cell line (SK-N-SH). Moreover, the efficacy of epothilone A was not impaired even though the Pgp level was further increased during treatment with the drug. |
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