Reversal of breast cancer resistance protein-mediated drug resistance by tryprostatin A |
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Authors: | Woehlecke Holger Osada Hiroyuki Herrmann Andreas Lage Hermann |
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Institution: | Institute of Biology/Biophysics, Humboldt University Berlin, Berlin, Germany. |
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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. |
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Keywords: | atypical multidrug resistance chemosensitizer MDR modulator diketopiperazine ABCG2 MXR |
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