TY - JOUR
T1 - Inhibition of ecto-ATPase activity by curcumin in hepatocellular carcinoma HepG2 cells
AU - Fujii, Takuto
AU - Minagawa, Takuma
AU - Shimizu, Takahiro
AU - Takeguchi, Noriaki
AU - Sakai, Hideki
N1 - Funding Information:
Acknowledgments This work was supported in part by Grants-in-Aid for Scientific Research 20056010 (to H.S.) and 22790204 (to T.F.) from the Japan Society for the Promotion of Science and Grants-in-Aid for Scientific Research 21390056 (to H.S.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
PY - 2012/1
Y1 - 2012/1
N2 - Effects of curcumin, a major constituent of turmeric, on ecto-nucleotidases have not been clarified. Here, we investigated whether curcumin affects ectonucleotidase 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-2,20-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.
AB - Effects of curcumin, a major constituent of turmeric, on ecto-nucleotidases have not been clarified. Here, we investigated whether curcumin affects ectonucleotidase 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-2,20-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.
KW - Curcumin
KW - Ecto-ATPase
KW - Extracellular ATP hydrolysis
KW - Hepatocellular carcinoma
KW - NTPDase
UR - http://www.scopus.com/inward/record.url?scp=84860339689&partnerID=8YFLogxK
U2 - 10.1007/s12576-011-0176-5
DO - 10.1007/s12576-011-0176-5
M3 - 学術論文
C2 - 21932081
AN - SCOPUS:84860339689
SN - 1880-6546
VL - 62
SP - 53
EP - 58
JO - Journal of Physiological Sciences
JF - Journal of Physiological Sciences
IS - 1
ER -