title: Reversal of breast cancer resistance protein-mediated drug resistance by tryprostatin A.
abstract: MDR in human cancers is one of the major causes of failure of chemotherapy. A member of the superfamily of ABC transporters, BCRP, was demonstrated to confer an atypical MDR phenotype to tumor cells. To overcome the BCRP-mediated drug resistance, the fungal secondary metabolite TPS-A, a diketopiperazine, was analyzed with regard to its potency to reverse the BCRP-mediated drug-resistant phenotype. At concentrations of 10-50 microM, TPS-A reversed a mitoxantrone-resistant phenotype and inhibited the cellular BCRP-dependent mitoxantrone accumulation in the human gastric carcinoma cell line EPG85-257RNOV, the human breast cancer cell line MCF7/AdrVp (both exhibiting acquired BCRP-mediated MDR) and the BCRP cDNA-transfected breast cancer cell line MCF-7/BCRP clone 8. No cytotoxicity was seen at effective concentrations. These data indicate that TPS-A is a novel BCRP inhibitor.
authors.affiliation: Institute of Biology/Biophysics, Humboldt University Berlin, Berlin, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Woehlecke
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Osada
authors.forename: Andreas
authors.initials: A
authors.lastname: Herrmann
authors.forename: Hermann
authors.initials: H
authors.lastname: Lage
mesh_terms: D000166:Acridines / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000633:toxicity*; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003630:Daunorubicin / Q000633:toxicity; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D005260:Female; D006801:Humans; D026121:Indole Alkaloids / Q000494:pharmacology*; D007700:Kinetics; D008942:Mitoxantrone / Q000633:toxicity; D010879:Piperazines / Q000494:pharmacology*; D013274:Stomach Neoplasms; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000166:Acridines; D000970:Antineoplastic Agents; D026121:Indole Alkaloids; D010879:Piperazines; D044005:Tetrahydroisoquinolines; C097858:tryprostatin A; D008942:Mitoxantrone; C083501:Elacridar; D003630:Daunorubicin