Growth‐Promoting Action of Adenosine‐Containing Dinucleotide on Neuroblastoma Cells: Detection of Adenosine‐Cytidine Dinucleotide (ApCp) in Neurofibroma (NF1) Extracts

Abstract: Neurofibroma type 1 tissue was investigated for the presence of growth‐promoting activity on human neuroblastoma cells. The activity was isolated by gel filtration and reversed‐phase column chromatographs from neurofibroma type 1 extracts. An adenosine‐containing dinucleotide (adenylyl(3′‐5′)cytidine‐3′‐phosphate) was identified as one of the major components of the activities by its enzymatic fragmentation and liquid chromatography/mass spectrometry. Synthetic adenosine‐containing dinucleotide derivatives such as cytidyl(3′‐5′)adenosine, cytidyl(2′‐5′)adenosine, adenylyl(3′‐5′)cytidine, and adenylyl(2′‐5′)cytidine showed a similar action. Cytidyl(3′‐5′)adenosine, cytidyl(2′‐5′)adenosine, and adenylyl(2′‐5′)cytidine, which are able to release a free adenosine through enzymatic hydrolysis, in particular elicited a strong activity corresponding to that of adenosine with the highest action. These results suggest that neuroblastoma cells are able to use adenosine‐containing dinucleotides as well as mononucleotides for their survival and proliferation.