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Growth Inhibition of Human Glioma Cells Induced by 8-Chloroadenosine, an Active Metabolite of 8-Chloro Cyclic Adenosine 3′:5′-Monophosphate

Cornelis H. Langeveld, Cornelis A. M. Jongenelen, Jan J. Heimans and Johannes C. Stoof
Cornelis H. Langeveld
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Cornelis A. M. Jongenelen
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Jan J. Heimans
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Johannes C. Stoof
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DOI:  Published July 1992
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Abstract

8-Chloroadenosine 3′:5′-monophosphate (8ClcAMP) inhibits the growth of human glioma cell lines at much lower concentrations than more commonly used cyclic AMP analogues, without inducing morphological differentiation. The mechanism by which 8ClcAMP exerts this effect is not fully understood. We examined whether the growth-inhibitory effect of this compound is due to an active metabolite, using a sulforhodamine protein stain assay to determine the proliferation rate of the WF human glioma cell line. 8-Chloroadenosine, one of the metabolites, inhibited the proliferation of WF human glioma cells more potently than 8ClcAMP. In the presence of adenosine deaminase, which converts 8-chloroadenosine into 8-chloroinosine, 8-chloroadenosine no longer inhibited human glioma cell growth. Addition of adenosine deaminase also largely reduced the growth-inhibitory effect of 8ClcAMP, but not of 8-(4-chlorophenylthio)cAMP. High performance liquid chromatography analysis revealed that at least part of the 8ClcAMP in the culture medium is converted into 8-chloroadenosine. We concluded that 8ClcAMP exerts its growth-inhibitory effect through its active metabolite 8-chloroadenosine. Adenylate cyclase assays showed that 8-chloroadenosine does not affect the intracellular cAMP production through adenosine A1 or A2 receptor activation, which makes it unlikely that 8-chloroadenosine inhibits glioma cell growth by increasing the intracellular cyclic AMP concentration.

Footnotes

  • ↵1 To whom requests for reprints should be addressed.

  • Received December 16, 1991.
  • Accepted May 7, 1992.
  • ©1992 American Association for Cancer Research.
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July 1992
Volume 52, Issue 14
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Growth Inhibition of Human Glioma Cells Induced by 8-Chloroadenosine, an Active Metabolite of 8-Chloro Cyclic Adenosine 3′:5′-Monophosphate
Cornelis H. Langeveld, Cornelis A. M. Jongenelen, Jan J. Heimans and Johannes C. Stoof
Cancer Res July 15 1992 (52) (14) 3994-3999;

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Growth Inhibition of Human Glioma Cells Induced by 8-Chloroadenosine, an Active Metabolite of 8-Chloro Cyclic Adenosine 3′:5′-Monophosphate
Cornelis H. Langeveld, Cornelis A. M. Jongenelen, Jan J. Heimans and Johannes C. Stoof
Cancer Res July 15 1992 (52) (14) 3994-3999;
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