2-ChloroATP exerts antitumoral actions not mediated by P2 receptors in neuronal and glial cell lines. (Articolo in rivista)

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  • 2-ChloroATP exerts antitumoral actions not mediated by P2 receptors in neuronal and glial cell lines. (Articolo in rivista) (literal)
Anno
  • 2004-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1016/j.bcp.2003.09.015 (literal)
Alternative label
  • D'Ambrosi N.1, Costanzi S.2, Angelini D.F.3, Volpini R.4, Sancesario G.5, Cristalli G.6, Volonté C.7 (2004)
    2-ChloroATP exerts antitumoral actions not mediated by P2 receptors in neuronal and glial cell lines.
    in Biochemical pharmacology
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • D'Ambrosi N.1, Costanzi S.2, Angelini D.F.3, Volpini R.4, Sancesario G.5, Cristalli G.6, Volonté C.7 (literal)
Pagina inizio
  • 621 (literal)
Pagina fine
  • 630 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#altreInformazioni
  • IF =3.436 SCI-JCR 2004 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 67 (literal)
Rivista
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  • 4 (literal)
Note
  • Scopu (literal)
  • ISI Web of Science (WOS) (literal)
  • PubMe (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1,7 = Fondazione Santa Lucia, Cellular Neurobiology Unit, Rome, Italy; 1,5 = Department of Neuroscience, University of Rome Tor Vergata, Rome, Rome, Italy; 2,4,6 = Department of Chemical Sciences, University of Camerino, Camerino Italy; 3 = Fondazione Santa Lucia, Neuroimmunology Unit, Rome, Italy; 7 = C.N.R., INMM, Rome, Italy. (literal)
Titolo
  • 2-ChloroATP exerts antitumoral actions not mediated by P2 receptors in neuronal and glial cell lines. (literal)
Abstract
  • We investigated the effects of the ATP analogue and P2 receptor agonist 2-ClATP on growth and survival of different neuronal (PC12, PC12nnr5 and SH-SY5Y) and glial (U87 and U373) cell lines, by the use of direct count of intact nuclei, fluorescence microscopy, fluorescence-activated cell sorter analysis (FACS) and high pressure liquid chromatography (HPLC). 2-ClATP lowered the number of cultured PC12nnr5, SH-SY5Y, U87 and U373 cells to almost 5%, and of PC12 cells to about 35% after 3-4 days of treatment. EC(50) was in the 5-25 microM range, with 2-ClATP behaving as a cytotoxic or cytostatic agent. Analysis of the biological mechanisms demonstrated that pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (P2 receptor antagonist and nucleotidases inhibitor), but not Caffeine or CGS-15493 (P1 receptor antagonists) effectively prevented 2-ClATP-induced toxicity. 2-ClATP metabolic products (2-ClADP, 2-ClAMP, 2-Cladenosine) and new synthesis derivatives (2-CldAMP, 2-Cldadenosine-3',5'-bisphosphate and 2-CldATP) exerted similar cytotoxic actions. Inhibition of both serum nucleotidases and purine nucleoside transporters strongly reduced 2-ClATP-induced cell death, which was conversely increased by the nucleotide hydrolyzing enzyme apyrase. The adenosine kinase inhibitor 5-iodotubericidin totally prevented 2-ClATP or 2-Cladenosine-induced toxicity. In summary, our findings indicate that 2-ClATP exerts either cell cycle arrest or cell death, acting neither on P2 nor on P1 receptors, but being extracellularly metabolized into 2-Cladenosine, intracellularly transported and re-phosphorylated. (literal)
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