| Induction of apoptosis dependent on caspase activities and growth arrest in HL-60 cells by PGA2. | |
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MedLine Citation:
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PMID: 12428687 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Prostaglandin (PG) A2 has been reported to inhibit the growth or induce apoptosis of various tumor cells. In the present study, PGA2 inhibited the growth of HL-60 cells and concomitantly-induced nuclear condensation and DNA fragmentation, characteristics of apoptosis. Down-regulation of c-myc mRNA, and activation of caspase-3 were observed in the PGA2 -treated cells. PGA2-induced DNA fragmentation was completely abolished in the presence of zVAD-Fmk or zDEVD-Fmk. But, relative cell survival was not improved up to that of untreated cells by pretreatment of caspase inhibitors, and c-myc down-regulation was not recovered by caspase inhibitors, either. Moreover, cytochrome c release and activation of caspase-9 was also observed in apoptotic cells and a specific inhibitor of caspase-9 (zLEHD-Fmk) prevented both DNA fragmentation and activation of caspase-3, but not relative cell survival, implying the upstream mitochondrial event of caspase-3 activation. In addition, antagonistic Fas antibody (ZB4) exerted no effect on the apoptosis. Taken together, these results suggest that PGA2 may induce the apoptosis as well as growth inhibition in HL-60 cells, and cytochrome c release and caspase activation seem to play a critical role in this apoptosis which might be independent or downstream of growth inhibition associated with c-myc down-regulation. |
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Authors:
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Ho-Shik Kim; Hyangshuk Rhim; Seong-Whan Jeong; Jin Woo Kim; In-Kyung Kim |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Prostaglandins & other lipid mediators Volume: 70 ISSN: 1098-8823 ISO Abbreviation: Prostaglandins Other Lipid Mediat. Publication Date: 2002 Sep |
Date Detail:
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Created Date: 2002-11-13 Completed Date: 2003-04-08 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9808648 Medline TA: Prostaglandins Other Lipid Mediat Country: United States |
Other Details:
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Languages: eng Pagination: 169-83 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, College of Medicine, Catholic University of Korea, Seoul, South Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Chloromethyl Ketones
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pharmacology Antibodies, Monoclonal Antigens, CD95 / immunology Apoptosis / drug effects, physiology* Caspases / metabolism* Cell Division / drug effects Cytochrome c Group / metabolism Down-Regulation Enzyme Activation Genes, myc / physiology HL-60 Cells Humans Oligopeptides / pharmacology Prostaglandins A / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Amino Acid Chloromethyl Ketones; 0/Antibodies, Monoclonal; 0/Antigens, CD95; 0/Cytochrome c Group; 0/Oligopeptides; 0/Prostaglandins A; 0/benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 13345-50-1/prostaglandin A2; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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