Cancer Chemotherapy and Pharmacology

, Volume 68, Issue 3, pp 603–610

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

  • Yan Li
  • Jezrael L. Revalde
  • Glen Reid
  • James W Paxton
Original Article

DOI: 10.1007/s00280-010-1515-6

Cite this article as:
Li, Y., Revalde, J.L., Reid, G. et al. Cancer Chemother Pharmacol (2011) 68: 603. doi:10.1007/s00280-010-1515-6

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.

Keywords

CurcuminMulti-drug resistance-associated protein 5Pancreatic cancer5-Fluorouracil

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Yan Li
    • 1
  • Jezrael L. Revalde
    • 1
  • Glen Reid
    • 1
    • 2
  • James W Paxton
    • 1
  1. 1.Department of Pharmacology & Clinical Pharmacology, School of Medical Sciences, Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand
  2. 2.The Asbestos Diseases Research Institute, Bernie Banton CentreUniversity of SydneySydneyAustralia