title: Inhibition of ecto-ATPase activity by curcumin in hepatocellular carcinoma HepG2 cells.
abstract: Effects of curcumin, a major constituent of  turmeric, on ecto-nucleotidases have not been clarified. Here, we investigated whether curcumin affects ecto-nucleotidase activities in human hepatocellular carcinoma HepG2 cells. In the cells, high levels of Mg(2+)-dependent activity of ecto-nucleotidases were observed in the presence of 1 mM adenosine triphosphate (ATP). The activity was inhibited by ecto-ATPase inhibitors such as suramin, ZnCl(2) and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid. On the other hand, the activity was significantly decreased at alkaline pH (pH 9) and was not inhibited by levamisole, an inhibitor of alkaline phosphatase. In the presence of ATP, curcumin inhibited the activity in a concentration-dependent manner (IC(50) = 6.2 μM). In contrast, curcumin had no effects on ecto-nucleotidase activity in the presence of ADP (1 mM) or AMP (1 mM). The K                         (m) value for ATP hydrolysis of curcumin-sensitive ecto-ATPase was similar to the value of NTPDase2, an isoform of ecto-nucleoside triphosphate diphosphohydrolase. These results suggest that curcumin is a potent inhibitor of ecto-ATPase and may affect extracellular ATP-dependent responses.
authors.affiliation: Department of Pharmaceutical Physiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan.
authors.forename: Takuto
authors.initials: T
authors.lastname: Fujii
authors.forename: Takuma
authors.initials: T
authors.lastname: Minagawa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shimizu
authors.forename: Noriaki
authors.initials: N
authors.lastname: Takeguchi
authors.forename: Hideki
authors.initials: H
authors.lastname: Sakai
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D002712:Chlorides / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D013498:Suramin / Q000494:pharmacology; D017967:Zinc Compounds / Q000494:pharmacology
chemical_list: D002712:Chlorides; D017967:Zinc Compounds; D013498:Suramin; C016837:zinc chloride; D000251:Adenosine Triphosphatases; C027201:ectoATPase; D008274:Magnesium; D003474:Curcumin; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid