Induction of apoptosis in human leukemia cells by 3-deazaadenosine is mediated by caspase-3-like activity
Experimental & Molecular Medicine
;
: 197-203, 2000.
Article
in English
| WPRIM
| ID: wpr-25123
ABSTRACT
3-Deazaadenosine (DZA), one of the potent inhibitors of S-adenosylhomocysteine hydrolase, is known to possess several biological properties including an induction of apoptosis. To evaluate a possibility that DZA may be utilized for the treatment of human leukemia, we studied molecular events of cell death induced by DZA in human leukemia HL-60 and U-937 cells. DZA induced a specific cleavage of poly ADP-ribose polymerase (PARP) and an activation of the cysteine protease caspase-3/CPP32 which is known to cleave PARP. DZA-mediated nuclear DNA-fragmentation was completely blocked in the presence of a universal inhibitor of caspases (z-VAD-fmk) or the specific inhibitor of caspase-3 (z-DEVD-fmk) unlike of cycloheximide (CHX). DNA fragmentation was preceded by the lowering of c-myc mRNA in the DZA treated cells. In addition, DZA-induced apoptosis was blocked by pretreatment with adenosine transporter inhibitors such as nitrobenzylthioinosine (NBTI) and dipyridamole (DPD). Taken together, these results demonstrate that DZA-induced apoptosis initiated through an active transport of DZA into human leukemia cells, is dependent on the caspase-3-like activity without de novo synthesis of proteins and possibly involves c-myc down-regulation.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Thioinosine
/
Transcription Factors
/
Biological Transport, Active
/
Tubercidin
/
Leukemia, Promyelocytic, Acute
/
Carrier Proteins
/
Down-Regulation
/
Adenosine
/
Genes, myc
/
Apoptosis
Limits:
Humans
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2000
Type:
Article
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