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: Holger Woehlecke, Hiroyuki Osada, Andreas Herrmann, Hermann Lage
• Journal: International journal of cancer (Int J Cancer) Vol. 107 Issue 5 Pg. 721-8 (Dec 10 2003) ISSN: 0020-7136 [Print] United States
• PMID: 14566821 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2003 Wiley-Liss, Inc.

Chemical References

• Acridines
• Antineoplastic Agents
• Indole Alkaloids
• Piperazines
• Tetrahydroisoquinolines
• tryprostatin A
• Mitoxantrone
• Elacridar
• Daunorubicin

Topics

• Acridines (pharmacology)
• Antineoplastic Agents (toxicity)
• Breast Neoplasms (pathology)
• Cell Division (drug effects)
• Daunorubicin (toxicity)
• Drug Resistance, Multiple (drug effects)
• Female
• Humans
• Indole Alkaloids (pharmacology)
• Kinetics
• Mitoxantrone (toxicity)
• Piperazines (pharmacology)
• Stomach Neoplasms
• Tetrahydroisoquinolines (pharmacology)
• Tumor Cells, Cultured