A. Wolff et al., EPOTHILONE-A INDUCES APOPTOSIS IN NEUROBLASTOMA-CELLS WITH MULTIPLE MECHANISMS OF DRUG-RESISTANCE, International journal of oncology, 11(1), 1997, pp. 123-126
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.