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Title of Journal: Cancer Chemother Pharmacol

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Abbravation: Cancer Chemotherapy and Pharmacology

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Springer-Verlag

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DOI

10.1007/s12288-014-0417-x

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1432-0843

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Modulatory effects of curcumin on multidrug resis

Authors: Yan Li Jezrael L Revalde Glen Reid James W Paxton
Publish Date: 2010/11/30
Volume: 68, Issue: 3, Pages: 603-610
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Abstract

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 firstline drugs 5fluorouracil and gemcitabine by active efflux of drugs from the cell Our aim was to evaluate whether curcumin could reverse this multidrug resistance by inhibition of MRP5mediated effluxMRP5 protein was detected and localized by immunocytochemistry using a monoclonal antibody in MRP5 overexpressing HEK293 HEK293/MRP5 cells and two pancreatic cancer cell lines PANC1 and MiaPaCa2 The cellular accumulation of a specific MRP5 fluorescent substrate 2′7′Bis2carboxyethyl56carboxyfluorescein BCECF into these cells was measured by flow cytometry and the cell proliferation determined by a 72h CyQuant assayThe cellular accumulation of BCECF in HEK293/MRP5 cells and in PANC1 and MiaPaCa2 cells was significantly increased by curcumin in a concentrationdependent 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 concentrationdependant increase in the sensitivity to the cytotoxic drug 5fluorouracil in HEK293/MRP5 cells PANC1 and MiaPaCa2 pancreatic cancer cells but not in parental HEK293 cells

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