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Cancer Chemother Pharmacol. 2011 Sep;68(3):603-10. doi: 10.1007/s00280-010-1515-6. Epub 2010 Nov 30.

Modulatory effects of curcumin on multi-drug resistance-associated protein 5 in pancreatic cancer cells.

Author information

  • 1Department of Pharmacology & Clinical Pharmacology, The University of Auckland, Auckland, New Zealand. yan.li@auckland.ac.nz

Abstract

PURPOSE:

Chemotherapy of pancreatic cancer often fails due to the development of intrinsic and acquired resistance during drug treatment. Recent studies have suggested that MRP5 conferred resistance to first-line drugs 5-fluorouracil and gemcitabine by active efflux of drugs from the cell. Our aim was to evaluate whether curcumin could reverse this multi-drug resistance by inhibition of MRP5-mediated efflux.

METHODS:

MRP5 protein was detected and localized by immunocytochemistry using a monoclonal antibody in MRP5 over-expressing HEK293 (HEK293/MRP5) cells and two pancreatic cancer cell lines PANC-1 and MiaPaCa-2. The cellular accumulation of a specific MRP5 fluorescent substrate 2',7'-Bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) into these cells was measured by flow cytometry and the cell proliferation determined by a 72-h CyQuant assay.

RESULTS:

The cellular accumulation of BCECF in HEK293/MRP5 cells and in PANC-1 and MiaPaCa-2 cells was significantly increased by curcumin in a concentration-dependent manner. Curcumin and a MRP5 inhibitor MK571 had no apparent effects on cellular accumulation of BCECF in parental HEK293 cells. In the proliferation assays, curcumin caused a concentration-dependant increase in the sensitivity to the cytotoxic drug 5-fluorouracil in HEK293/MRP5 cells, PANC-1 and MiaPaCa-2 pancreatic cancer cells, but not in parental HEK293 cells.

CONCLUSIONS:

Our results suggest that curcumin is an inhibitor of MRP5 and may be useful in the reversal of multi-drug resistance in pancreatic cancer chemotherapy.

PMID:
21116627
[PubMed - indexed for MEDLINE]
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