The effect of pyrimidine nucleosides on adenosine-induced apoptosis in HL-60 cells.
Among several nucleosides, adenosine is the only one to induce typical apoptotic cell death in human promyelocytic leukemia HL-60 cells. Intracellularly transported adenosine seemed to be required for the induction of apoptosis, since dipyridamole, which inhibits the transport of adenosine, strongly suppressed apoptosis, and 8-phenyltheophylline, a receptor antagonist, did not affect the adenosine-induced effect. The viability of adenosine-treated HL-60 cells was partially recovered by supplementation with a pyrimidine nucleoside, uridine or thymidine. Cytidine or deoxycytidine had no effect on the growth and survival of adenosine-treated cells, while uridine or thymidine inhibited adenosine-induced intracellular DNA fragmentation. These results suggest that the quantitative adjustment of purine and pyrimidine nucleosides might play an important role in the adenosine-induced apoptosis of HL-60 cells. The reduction of c-Myc expression in adenosine-treated cells was prevented by uridine or thymidine. These observations suggest that the expression of c-Myc might be related to an intracellular sensing system for the quantitative balance of nucleosides or nucleotides.
Kim
K T
KT
Department of Food and Nutrition, College of Human Ecology, Seoul National University, Korea.
Yeo
E J
EJ
Choi
H
H
Park
S C
SC
D000241:Adenosine / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053938:DNA Fragmentation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D004176:Dipyridamole / Q000494:pharmacology; D004587:Electrophoresis, Agar Gel; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000187:drug effects; D011741:Pyrimidine Nucleosides / Q000494:pharmacology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D004273:DNA, Neoplasm; D016271:Proto-Oncogene Proteins c-myc; D011741:Pyrimidine Nucleosides; D004176:Dipyridamole; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine