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
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  • Published online on: February 14, 2019     https://doi.org/10.3892/or.2019.7011
  • Pages: 2558-2566
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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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April-2019
Volume 41 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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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