Purine Nucleoside-dependent inhibition of cellular proliferation in 1321N1 human astrocytoma cells

Florian Islinger, Michael Gekle, Stephen Wright

Research output: Contribution to journalArticle

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Abstract

We examined the effects of purines and the pyrimidine UTP on cellular proliferation in the human astrocytoma cell line 1321N1. Treatment of cultured cells with 100 μM ATP or 2-chloroadenosine (2-CA) resulted in significant reductions in cell numbers after 2 days, whereas adenosine (ADO) exhibited a slower time course of inhibition of cell growth. Treatment with 100 μM UTP had no effect on cell numbers. 2-Chloroadenosine but neither ATP nor ADO resulted in an increase in cell death rates. A significant portion of the inhibitory response to ATP, ADO, or 2-CA was sensitive to the purine nucleoside transport inhibitor S-(p-nitrobenzyl)-6-thioguanosine, suggesting that uptake into cells was required for the inhibitory response. At least the majority of the observed responses to purines was not mediated by P1 (adenosine) receptors, because effects of ATP, ADO, or 2-CA were not affected by treatment of cells with the P1 receptor antagonist 8-(p-sulfophenyl)-theophylline. The absence of any known P2 (nucleotide) receptors in 1321N1 cells, coupled with the failure of the relatively stable ATP analog adenosine 5′-O-(3-thiotriphosphate) to alter cell growth rates, suggests that ATP acts indirectly to inhibit proliferation via one or more metabolic products. Although intracellular effects of purine nucleosides should be taken into account in future studies using 1321N1 cells, our findings also suggest 1321N1 cells as an excellent model for intracellular actions of nucleosides.

Original languageEnglish (US)
Pages (from-to)748-752
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume299
Issue number2
StatePublished - 2001

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Purine Nucleosides
Astrocytoma
2-Chloroadenosine
Cell Proliferation
Adenosine Triphosphate
Adenosine
Purines
Uridine Triphosphate
Cell Count
Purinergic P1 Receptors
Growth
Nucleosides
Cultured Cells
Cell Death
Nucleotides
Cell Line
Mortality

ASJC Scopus subject areas

  • Pharmacology

Cite this

Purine Nucleoside-dependent inhibition of cellular proliferation in 1321N1 human astrocytoma cells. / Islinger, Florian; Gekle, Michael; Wright, Stephen.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 299, No. 2, 2001, p. 748-752.

Research output: Contribution to journalArticle

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