Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice

Suneet Shukla, Hani Zaher, Anika Hartz, Björn Bauer, Joseph A. Ware, Suresh V. Ambudkar

Research output: Contribution to journalArticlepeer-review

126 Scopus citations


Purpose. To evaluate the in vivo efficacy of curcumin as an inhibitor of the multidrug-resistance-linked ATP Binding Cassette (ABC) drug transporter, ABCG2. Methods. Photoaffinity labeling with [125I]- iodoarylazidoprazosin was used to characterize the interaction of sulfasalazine, a substrate of the mouse ABCG2, with human ABCG2. In addition, the inhibitory effect of curcumin on ABCG2 was evaluated in brain capillaries from rats. Furthermore, the effect of curcumin on absorption of orally administered sulfasalazine in wild-type and abcg2 -/- mice was also determined. Results. Sulfasalazine interacted at the drug-substrate site(s) of human ABCG2. Curcumin inhibited ABCG2 activity at nanomolar concentrations at the rat blood-brain barrier in the ex vivo assay. Based on studies in wild type and abcg2 -/- mice, we observed that oral curcumin increased C max and relative bioavailability of sulfasalazine by selectively inhibiting ABCG2 function. Conclusions. This study validates our previous in vitro results with human ABCG2 (Chearwae et al., Mol. Cancer Ther. 5:1995-2006, 2006) and provides the first in vivo evidence for the inhibition by curcumin of ABCG2-mediated efflux of sulfasalazine in mice. Based on these studies, we propose that non-toxic concentrations of curcumin may be used to enhance drug exposure when the rate-limiting step of drug absorption and/or tissue distribution is impacted by ABCG2.

Original languageEnglish
Pages (from-to)480-487
Number of pages8
JournalPharmaceutical Research
Issue number2
StatePublished - Feb 2009

Bibliographical note

Funding Information:
This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. We thank Dr. Krishnamachary Nandigama for providing ABCG2-expressing Hi-five insect cell crude membranes and George Leiman for editorial assistance. The authors wish to acknowledge the contribution of Joe Palandra of Pfizer Global Research and Development for his assistance in determination of SASP bioanalysis and for the input of Lisa Bernstein, Nonclinical Biostatistics, Genentech, Inc.


  • ABC transporter
  • ABCG2
  • Curcumin
  • Multidrug resistance
  • Sulfasalazine

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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