Guanosine acts intracellularly to initiate apoptosis in NB4 cells: A role for nucleoside transport.
Guanosine initiated apoptosis in NB4 cells in a transport-dependent manner. Apoptosis was partially attributed to an imbalance in nucleosides with some protection upon the addition of pyrimidines. The effect of guanosine on cell proliferation and viability was biphasic whereby cells were able to recover from an initial cell cycle arrest and re-enter the cell cycle upon removal of guanosine in a time-dependent fashion. However, exposure to guanosine beyond 24 h prevented recovery and ultimately led to death. Death occurred with a decrease in bcl-2 protein expression, thus suggesting that the pathway to apoptosis involved change(s) in the intracellular environment that were ultimately sensed by the mitochondria. Expression of the unique guanosine-specific nucleoside transporter csg in NB4 cells may provide an opportunity to harness guanosine-mediated cell death in the treatment of APL and related malignancies while sparing normal cells.
Flanagan
Sheryl A
SA
Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada. sflan@umich.edu
Gandhi
Varsha
V
Meckling
Kelly A
KA
D017209:Apoptosis / Q000187:drug effects*; D001692:Biological Transport; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000032:analysis; D053938:DNA Fragmentation; D004176:Dipyridamole / Q000494:pharmacology; D006151:Guanosine / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011743:Pyrimidines / Q000494:pharmacology