title: Metabolism of Curcumin in Human Breast Cancer Cells: Impact of Sulfation on Cytotoxicity.
abstract: Curcumin is a natural polyphenol with promising anticancer properties that undergoes pronounced metabolism in humans. In order to determine whether metabolism of curcumin also occurs in tumor cells and whether biotransformation has any impact on cytotoxicity, metabolism experiments were conducted with hormone-dependent ZR-75-1 and hormone-independent MDA-MB-231 human breast cancer cells. By using HPLC-ESI-Qq-TOF-MS, it was possible to identify one main metabolite, namely curcumin sulfate, in both cell lines. Its concentration in the cytoplasm and culture medium was 1.6- to 1.7-fold higher in ZR-75-1 cells than in MDA-MB-231 cells, concomitant with a 2-fold higher IC50value in the ZR-75-1 cell line (14 µM compared to 7.3 µM). The net result of sulfation seems to lower the intracellular concentration of curcumin, thereby decreasing its growth inhibitory activity. Interestingly, for the first time, we also found the formation of a curcumin dimer in the cytoplasm but not in the cellular medium of both cell lines. Compared to curcumin sulfate, however, its maximal intracellular concentrations were up to 4-fold lower, indicating only a minor contribution to the overall curcumin clearance. In conclusion, our data elucidated the metabolism of curcumin in breast cancer cells, which must be considered in humans following oral uptake of dietary curcumin as a chemopreventive agent.
authors.affiliation: Department of Pharmaceutical Chemistry, Division of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria.
authors.forename: Qurrat Ul Ain
authors.initials: QUA
authors.lastname: Jamil
authors.affiliation: Department of Pharmaceutical Chemistry, Division of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria.|Research Group for Pharmaceutical Activities of Natural Products Using Pharmaceutical Biotechnology (PANPB), Faculty of Pharmaceutical Sciences, Khon Kean University, Khon Kaen, Thailand.
authors.forename: Natharath
authors.initials: N
authors.lastname: Jaerapong
authors.affiliation: Department of Pharmacognosy, University of Vienna, Vienna, Austria.|Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Zehl
authors.affiliation: Research Group for Pharmaceutical Activities of Natural Products Using Pharmaceutical Biotechnology (PANPB), Faculty of Pharmaceutical Sciences, Khon Kean University, Khon Kaen, Thailand.
authors.forename: Kanokwan
authors.initials: K
authors.lastname: Jarukamjorn
authors.affiliation: Department of Pharmaceutical Chemistry, Division of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Jäger
mesh_terms: D001711:Biotransformation; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D003474:Curcumin / Q000737:chemistry / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D013997:Time Factors
chemical_list: D004967:Estrogens; D003474:Curcumin