| 17568578 |
Bernardi A, Bavaresco L, Wink MR, Jacques-Silva MC, Delgado-Canedo A, Lenz G, Battastini AM: Indomethacin stimulates activity and expression of ecto-5'-nucleotidase/CD73 in glioma cell lines. Eur J Pharmacol. 2007 Aug 13;569(1-2):8-15. Epub 2007 May 22.
Gliomas are the most common and devastating primary tumors of the central nervous system. Ecto-NTPDases and ecto-5'-nucleotidase/CD73 can control extracellular ATP/adenosine levels, which have been described as proliferation factors. Here, we investigate the influence of indomethacin on the enzyme cascade that catalyses the interconversion of purine nucleotides in U138-MG and C6 glioma cell lines. Exposure of glioma cells to 100 microM indomethacin for 48 h caused increases of 52% (P < 0.05) and 62% (P < 0.05) in the AMP hydrolysis rate in C6 and U138-MG cell lines, respectively. Indomethacin treatments also increased ATP hydrolysis. Significant increase in ecto-5'-nucleotidase/CD73 mRNA and protein levels were observed after treatment with indomethacin. Pretreatment of glioma cells with a specific antagonist of the adenosine A (3) receptor, MRS1220 (1 microM; 9-Chloro-2-(2-furanyl)-5-((phenylacetyl) amino)-[1,2,4] triazolo [1,5-c] quina zoline), significantly reduced the inhibition of cell proliferation induced by indomethacin. In addition, a significant increase in mRNA levels of the adenosine A (3) receptor was observed after treatment with indomethacin. In conclusion, our data indicate that adenosine A (3) receptors and the enzyme, ecto-5'-nucleotidase/CD73, are involved in the anti-proliferative effect of indomethacin in glioma cells. |
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