title: Differential cellular uptake and metabolism of curcuminoids in monocytes/macrophages: regulatory effects on lipid accumulation.
abstract: We have previously shown that curcumin (CUR) may increase lipid accumulation in cultured human acute monocytic leukaemia cell line THP-1 monocytes/macrophages, but that tetrahydrocurcumin (THC), an in vivo metabolite of CUR, has no such effect. In the present study, we hypothesised that the different cellular uptake and/or metabolism of CUR and THC might be a possible explanation for the previously observed differences in their effects on lipid accumulation in THP-1 monocytes/macrophages. Chromatography with tandem MS revealed that CUR was readily taken up by THP-1 monocytes/macrophages and slowly metabolised to hexahydrocurcumin sulphate. By contrast, the uptake of THC was low. In parallel with CUR uptake, increased lipid uptake was observed in THP-1 macrophages but not with the uptake of THC or another CUR metabolite and structurally related compounds. From these results, it is possible to deduce that CUR and THC are taken up and metabolised differently in THP-1 cells, which determine their biological activity. The remarkable differential cellular uptake of CUR, relative to THC and other similar molecules, may imply that the CUR uptake into cells may occur via a transporter.
authors.affiliation: Vascular Biology Laboratory, Jean Mayer USDA-Human Nutrition Research Center on Aging, Tufts University,Boston,MA02111,USA.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Vascular Biology Laboratory, Jean Mayer USDA-Human Nutrition Research Center on Aging, Tufts University,Boston,MA02111,USA.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Zingg
authors.affiliation: Vascular Biology Laboratory, Jean Mayer USDA-Human Nutrition Research Center on Aging, Tufts University,Boston,MA02111,USA.
authors.forename: Sharon H
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Vascular Biology Laboratory, Jean Mayer USDA-Human Nutrition Research Center on Aging, Tufts University,Boston,MA02111,USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thomas
authors.affiliation: Mass Spectrometry Laboratory, Jean Mayer USDA-Human Nutrition Research Center on Aging, Tufts University,Boston,MA,02111,USA.
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Dolnikowski
authors.affiliation: Vascular Biology Laboratory, Jean Mayer USDA-Human Nutrition Research Center on Aging, Tufts University,Boston,MA02111,USA.
authors.forename: Angelo
authors.initials: A
authors.lastname: Azzi
authors.affiliation: Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University,Sendai981-8555,Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Miyazawa
authors.affiliation: Vascular Biology Laboratory, Jean Mayer USDA-Human Nutrition Research Center on Aging, Tufts University,Boston,MA02111,USA.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Meydani
mesh_terms: D001692:Biological Transport; D002273:Carcinogens / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D036381:Diarylheptanoids; D020719:Glucuronides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D050356:Lipid Metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013431:Sulfates / Q000737:chemistry / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D002273:Carcinogens; D036381:Diarylheptanoids; D020719:Glucuronides; D013431:Sulfates; C569902:hexahydrocurcumin; C096277:tetrahydrocurcumin; C034786:bisdemethoxycurcumin; C016658:phorbolol myristate acetate; C000591193:curcumin glucuronide; D003474:Curcumin; D013755:Tetradecanoylphorbol Acetate; C050229:demethoxycurcumin