Correlation of intracellular diadenosine triphosphate (Ap3 A) with apoptosis in Fhit-positive HEK293 cells

• Published in: Cancer letters Vol. 259; no. 2; pp. 186 - 191
• Main Authors: Fisher, David I, McLennan, Alexander G
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 08-02-2008; Elsevier Limited
• Subjects: Acetates - pharmacology; Acid Anhydride Hydrolases - metabolism; Antibodies; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Apoptosis - drug effects; Cadmium - pharmacology; Cell Line; Cold Temperature; Diadenosines; Dinucleoside Phosphates - metabolism; Epithelial Cells - drug effects; Epithelial Cells - immunology; Epithelial Cells - metabolism; Epithelial Cells - pathology; Etoposide - pharmacology; fas Receptor - immunology; FHIT; Hematology, Oncology and Palliative Medicine; Humans; Kinases; Lasers; Ligands; Microscopy; Neoplasm Proteins - metabolism; Osmotic Pressure; Phosphorylation; Proteins; Signal transduction; Signal Transduction - drug effects; Sorbitol - pharmacology; Tumor suppression; Up-Regulation; Diadenosines; Tumor suppression; FHIT; Apoptosis
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2007.10.007

Abstract The pro-apoptotic Fhit tumor suppressor protein binds and hydrolyses diadenosine triphosphate (Ap3 A) and diadenosine tetraphosphate (Ap4 A) in vitro . We have measured the level of both these nucleotides in Fhit-positive HEK293 cells exposed to various apoptosis inducers. Cold shock, anti-Fas, cadmium ions and etoposide all increased the basal level of Ap4 A of 0.500 pmol/106 cells by about 50%. However, the corresponding increases in Ap3 A from a basal 0.079 pmol/106 cells correlated closely with the degree of apoptosis produced, up to a maximum of 0.510 pmol/106 cells with etoposide. These results support the view that Ap3 A is the in vivo Fhit ligand and that an inhibition of Fhit activity is a key element in Fhit-mediated apoptosis.