Antiproliferative effects induced by guanine-based purines require hypoxanthine-guanine phosphoribosyltransferase activity.
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.
Garozzo
Roberta
R
Department of Chemical Sciences, Section of Biochemistry, University of Catania, I-95125 Catania, Italy.
Sortino
Maria Angela
MA
Vancheri
Carlo
C
Condorelli
Daniele Filippo
DF
D049109:Cell Proliferation / Q000187:drug effects; D003124:Colorimetry; D006147:Guanine / Q000737:chemistry*; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism*; D011687:Purines / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D011687:Purines; D006147:Guanine; D007041:Hypoxanthine Phosphoribosyltransferase