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Article

Organic anion‑transporting polypeptides contribute to the uptake of curcumin and its main metabolites by human breast cancer cells: Impact on antitumor activity

  • Authors:
    • Nattharat Jaerapong
    • Qurratul Ain Jamil
    • Juliane Riha
    • Daniela Milovanovic
    • Georg Krupitza
    • Bruno Stieger
    • Kanokwan Jarukomjorn
    • Walter Jäger
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Pharmacy and Diagnostics, University of Vienna, A‑1090 Vienna, Austria, Department of Clinical Pathology, Medical University of Vienna, Vienna A‑1090, Austria, Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, 8091 Zurich, Switzerland, Research Group for Pharmaceutical Activities of Natural Products using Pharmaceutical Biotechnology (PANPB), Faculty of Pharmaceutical Sciences, Khon Kean University, Khon Kaen 40002, Thailand
  • Pages: 2558-2566
    |
    Published online on: February 14, 2019
       https://doi.org/10.3892/or.2019.7011
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Abstract

Curcumin is a natural polyphenolic compound with pronounced anticancer properties, despite its low bioavailability caused by extensive glucuronidation and sulfation. Information on the cellular uptake mechanisms and their contribution to the anticancer effects of curcumin and its biotransformation products is limited. The present study, therefore, investigated the role of organic anion‑transporting polypeptides (OATPs) in the cellular uptake of curcumin and its major metabolites in OATP‑expressing Chinese hamster ovary (CHO) and human ZR‑75‑1 breast cancer cells. The uptake rates for curcumin in OATP1B1‑, OATP1B3‑ and OATP2B1‑transfected CHO cells were 2‑ to 3‑fold higher than wild‑type cells. Curcumin sulfate was transported by all three OATPs, although to a much lesser extent, while uptake of tetrahydrocurcumin was the highest but only via OATP1B1 and OATP1B3. Notably, curcumin glucuronide did not exhibit any affinity for these OATPs. The increased mRNA levels of OATP1B1 in wild‑type human breast cancer ZR‑75‑1 cells compared with OATP1B1 knockdown cells was associated with a higher initial uptake of curcumin and tetrahydrocurcumin leading to decreased IC50 values. In conclusion, our data revealed that OATPs act as cellular uptake transporters for curcumin and its major metabolites, and this may also be applicable to patients undergoing cancer therapy.
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Copy and paste a formatted citation
Spandidos Publications style
Jaerapong N, Jamil QA, Riha J, Milovanovic D, Krupitza G, Stieger B, Jarukomjorn K and Jäger W: Organic anion‑transporting polypeptides contribute to the uptake of curcumin and its main metabolites by human breast cancer cells: Impact on antitumor activity. Oncol Rep 41: 2558-2566, 2019.
APA
Jaerapong, N., Jamil, Q.A., Riha, J., Milovanovic, D., Krupitza, G., Stieger, B. ... Jäger, W. (2019). Organic anion‑transporting polypeptides contribute to the uptake of curcumin and its main metabolites by human breast cancer cells: Impact on antitumor activity. Oncology Reports, 41, 2558-2566. https://doi.org/10.3892/or.2019.7011
MLA
Jaerapong, N., Jamil, Q. A., Riha, J., Milovanovic, D., Krupitza, G., Stieger, B., Jarukomjorn, K., Jäger, W."Organic anion‑transporting polypeptides contribute to the uptake of curcumin and its main metabolites by human breast cancer cells: Impact on antitumor activity". Oncology Reports 41.4 (2019): 2558-2566.
Chicago
Jaerapong, N., Jamil, Q. A., Riha, J., Milovanovic, D., Krupitza, G., Stieger, B., Jarukomjorn, K., Jäger, W."Organic anion‑transporting polypeptides contribute to the uptake of curcumin and its main metabolites by human breast cancer cells: Impact on antitumor activity". Oncology Reports 41, no. 4 (2019): 2558-2566. https://doi.org/10.3892/or.2019.7011
Copy and paste a formatted citation
x
Spandidos Publications style
Jaerapong N, Jamil QA, Riha J, Milovanovic D, Krupitza G, Stieger B, Jarukomjorn K and Jäger W: Organic anion‑transporting polypeptides contribute to the uptake of curcumin and its main metabolites by human breast cancer cells: Impact on antitumor activity. Oncol Rep 41: 2558-2566, 2019.
APA
Jaerapong, N., Jamil, Q.A., Riha, J., Milovanovic, D., Krupitza, G., Stieger, B. ... Jäger, W. (2019). Organic anion‑transporting polypeptides contribute to the uptake of curcumin and its main metabolites by human breast cancer cells: Impact on antitumor activity. Oncology Reports, 41, 2558-2566. https://doi.org/10.3892/or.2019.7011
MLA
Jaerapong, N., Jamil, Q. A., Riha, J., Milovanovic, D., Krupitza, G., Stieger, B., Jarukomjorn, K., Jäger, W."Organic anion‑transporting polypeptides contribute to the uptake of curcumin and its main metabolites by human breast cancer cells: Impact on antitumor activity". Oncology Reports 41.4 (2019): 2558-2566.
Chicago
Jaerapong, N., Jamil, Q. A., Riha, J., Milovanovic, D., Krupitza, G., Stieger, B., Jarukomjorn, K., Jäger, W."Organic anion‑transporting polypeptides contribute to the uptake of curcumin and its main metabolites by human breast cancer cells: Impact on antitumor activity". Oncology Reports 41, no. 4 (2019): 2558-2566. https://doi.org/10.3892/or.2019.7011
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