| Role of caspases and CD95/Fas in the apoptotic effects of a nucleotide analog PMEG in CCRF-CEM cells. | |
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MedLine Citation:
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PMID: 20683014 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND/AIM: 9-[2-(phosphonomethoxy)ethyl] guanine (PMEG) is a guanine acyclic nucleotide analog whose targeted prodrugs are being investigated for chemotherapy of lymphomas. Its antiproliferative effects have been attributed to cell cycle arrest and induction of apoptosis, however, the underlying mechanisms remain poorly understood. The objective of this study was to determine the requirements for caspase and CD95/Fas activation in PMEG-induced apoptosis. Additionally, the influence of PMEG on cell cycle regulatory proteins was explored. MATERIALS AND METHODS: CCRF-CEM cells were exposed to PMEG with/without caspase inhibitor or anti-Fas blocking antibody and assayed for phosphatidyl serine externalization, mitochondrial depolarization and the cleavage of procaspase 3 and the nuclear protein poly (ADP-ribose) polymerase (PARP). RESULTS: Despite an observed increase of caspase 3, 8 and 9 proteolytic activity, neither pretreatment of the cells with cell-permeable caspase inhibitors nor blocking the death receptor with anti-Fas antibody did prevent apoptosis induced by PMEG. CONCLUSION: PMEG-induced apoptosis is caspase- and CD95/Fas-independent. |
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Authors:
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Helena Mertlíková-Kaiserová; Ivan Votruba; Marika Matousová; Antonín Holy; Miroslav Hájek |
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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: Anticancer research Volume: 30 ISSN: 1791-7530 ISO Abbreviation: Anticancer Res. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-08-04 Completed Date: 2010-08-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8102988 Medline TA: Anticancer Res Country: Greece |
Other Details:
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Languages: eng Pagination: 2791-8 Citation Subset: IM |
Affiliation:
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Institute of Organic Chemistry and Biochemistry AS CR, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, CD95
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metabolism* Apoptosis / drug effects*, physiology Caspases / metabolism* Cell Cycle / drug effects, physiology Cell Line, Tumor Cyclin E / biosynthesis, genetics Cyclin-Dependent Kinase Inhibitor Proteins / biosynthesis, metabolism Cyclin-Dependent Kinases / biosynthesis, metabolism Dose-Response Relationship, Drug Enzyme Activation Guanine / analogs & derivatives*, pharmacology Humans Membrane Potential, Mitochondrial / drug effects Mitochondria / drug effects, physiology Oncogene Proteins / biosynthesis, genetics Organophosphorus Compounds / pharmacology* S Phase / drug effects Signal Transduction T-Lymphocytes / cytology, drug effects*, enzymology, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD95; 0/CCNE1 protein, human; 0/Cyclin E; 0/Cyclin-Dependent Kinase Inhibitor Proteins; 0/FAS protein, human; 0/Oncogene Proteins; 0/Organophosphorus Compounds; 114088-58-3/9-((2-phosphonylmethoxy)ethyl)guanine; 73-40-5/Guanine; EC 2.7.11.22/Cyclin-Dependent Kinases; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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