Inhibition of hepatoma cell growth by analogs of adenosine and cyclic AMP and the influence of enzymes in mammalian sera

✍ Scribed by James L. Hargrove; Daryl K. Granner

• Publisher: John Wiley and Sons
• Year: 1982
• Tongue: English
• Weight: 1004 KB
• Volume: 111
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041110303

✦ Synopsis

Abstract

The following evidence suggests that inhibition of hepatoma cell (HTC) growth by cyclic nucleotides is an adenosine‐like effect that is greatly modified by the type and treatment of serum used in the culture medium and is probably not mediated by cyclic AMP‐dependent protein kinase: (1) Heating serum reduces its phospho‐diesterase content, thereby slowing metabolism of cyclic AMP and reducing the inhibition of HTC cell growth by cyclic AMP; (2) Using medium that contains phosphodiesterase but lacks adenosine deaminase causes adenosine to accumulate from cyclic AMP and increases the toxicity of cyclic AMP; 3) Uridine or cytidine reverse the growth inhibition caused by adenosine, 5'‐AMP or cyclic AMP; 4) adenosine, 5'‐AMP and N^6^ ‐(δ^2^‐isopentenyl) adenosine are more toxic for HTC cells than is cyclic AMP, and N^6^, O^2^‐dibutyryl cyclic AMP is not toxic; and 5) N^6^, O^2^'‐dibutyryl cyclic AMP inhibits growth of Reuber H35 cells, but uridine prevents this inhibition of growth. We conclude that most, if not all, of the inhibitory effects of cyclic AMP and N^6^, O^2^'‐dibutyryl cyclic AMP on HTC and Reuber H35 hepatoma cell growth are due to the generation of toxic metabolites.