EPOTHILONE-A INDUCES APOPTOSIS IN NEUROBLASTOMA-CELLS WITH MULTIPLE MECHANISMS OF DRUG-RESISTANCE

Epothilone A, a novel macrolide antibiotic, is produced by the myxobac terium Sorangium cellulosum. Similarly to paclitaxel (Taxol), epothilo ne A inhibits cell proliferation and induces apoptosis by binding to t ubulin and stabilizing of microtubuli. Like paclitaxel, epothilone A i nduced apoptosis in neuroblastoma cells which exhibit constitutive cyt oplasmic sequestration of p53 and, hence, an impaired DNA-damage-depen dent apoptosis. However, in contrast to paclitaxel, epothilone A was a lso effective against a constitutively Pgp-expressing, multidrug resis tant neuroblastoma cell line (SK-N-SH). Moreover, the efficacy of epot hilone A was not impaired even though the Pgp level was further increa sed during treatment with the drug.