TY - JOUR
T1 - Organic anion‑transporting polypeptides contribute to the uptake of curcumin and its main metabolites by human breast cancer cells
T2 - Impact on antitumor activity
AU - Jaerapong, Nattharat
AU - Jamil, Qurratul Ain
AU - Riha, Juliane
AU - Milovanovic, Daniela
AU - Krupitza, Georg
AU - Stieger, Bruno
AU - Jarukomjorn, Kanokwan
AU - Jäger, Walter
N1 - Publisher Copyright:
© 2019 Spandidos Publications. All Rights Reserved.
PY - 2019/4
Y1 - 2019/4
N2 - 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.
AB - 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.
KW - Animals
KW - Antineoplastic Agents/metabolism
KW - Breast Neoplasms/drug therapy
KW - CHO Cells
KW - Cell Survival/drug effects
KW - Cricetulus
KW - Curcumin/metabolism
KW - Gene Knockdown Techniques
KW - Humans
KW - Organic Anion Transporters/genetics
KW - Cytotoxicity
KW - Breast cancer
KW - OATP
KW - Metabolism
KW - Curcumin
KW - Transport
UR - http://www.scopus.com/inward/record.url?scp=85062272175&partnerID=8YFLogxK
U2 - 10.3892/or.2019.7011
DO - 10.3892/or.2019.7011
M3 - Article
C2 - 30816509
SN - 1021-335X
VL - 41
SP - 2558
EP - 2566
JO - Oncology Reports
JF - Oncology Reports
IS - 4
ER -