Reversal of breast cancer resistance protein–mediated drug resistance by tryprostatin A

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 diketopipera...

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Bibliographic Details
Published in:International journal of cancer 2003-12, Vol.107 (5), p.721-728
Main Authors: Woehlecke, Holger, Osada, Hiroyuki, Herrmann, Andreas, Lage, Hermann
Format: Article
Language:English
Subjects:
ABCG2
Acridines - pharmacology
Antineoplastic agents
Antineoplastic Agents - toxicity
atypical multidrug resistance
Biological and medical sciences
Breast Neoplasms - pathology
Cell Division - drug effects
chemosensitizer
Daunorubicin - toxicity
diketopiperazine
Drug Resistance, Multiple - drug effects
Female
General aspects
Humans
Indole Alkaloids - pharmacology
Kinetics
MDR modulator
Medical sciences
Mitoxantrone - toxicity
MXR
Pharmacology. Drug treatments
Piperazines - pharmacology
Stomach Neoplasms
Tetrahydroisoquinolines - pharmacology
Tumor Cells, Cultured
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Summary: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 μM, 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. © 2003 Wiley‐Liss, Inc.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.11444