Antiproliferative effects induced by guanine-based purines require hypoxanthine-guanine phosphoribosyltransferase activity
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Roberta Garozzo
Abstract
Guanine (GUA), guanosine and GMP exert a marked growth inhibition on the U87 glioma cell line that is not seen with other tested nucleotides, nucleosides and nucleobases. This effect could be replicated in several different human tumoral cell lines. Guanine shows a higher potency than guanosine or GMP, and co-treatments with adenosine or adenine are able to antagonize or revert the antiproliferative effect of guanine. The loss of the guanine effect in a cell line bearing a mutated inactive hypoxanthine-guanine phosphoribosyltransferase (HGPRT), and the decreased potency of GUA in U87 cells silenced for HGPRT transcripts, demonstrates the central role of the intracellular metabolism of GUA for growth-inhibitory effects. Considering the potential application of growth-inhibitory substances in anticancer therapy, knowledge of the molecular mechanism underlying GUA-induced effects encourages studies aimed at defining possible tumoral targets for experimental therapies.
©2010 by Walter de Gruyter Berlin New York
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- Review
- Molecular mechanisms of signal transduction via adiponectin and adiponectin receptors
- Genes and Nucleic Acids
- Isolation of genes involved in pancreas regeneration by subtractive hybridization
- Wild type p53-dependent transcriptional upregulation of cathepsin L expression is mediated by C/EBPα in human glioblastoma cells
- Protein Structure and Function
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- Membranes, Lipids, Glycobiology
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- Cell Biology and Signaling
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- Phosphorylation of caldesmon by myosin light chain kinase increases its binding affinity for phosphorylated myosin filaments
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