| Retinoic acid reduces the cytotoxicity of cyclopentenyl cytosine in neuroblastoma cells. | |
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MedLine Citation:
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PMID: 12220665 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In this paper, it is demonstrated that all-trans, 9-cis and 13-cis retinoic acid (RA) decreased the sensitivity of SK-N-BE(2)c neuroblastoma cells towards the chemotherapeutic agent cyclopentenyl cytosine (CPEC), a potent inhibitor of cytosine-5'-triphosphate synthetase. Retinoic acid attenuated CPEC-induced apoptosis as reflected by a decreased caspase-3 induction. Retinoic acid decreased the accumulation of CPEC, whereas the salvage of cytidine was strongly increased. Metabolic labeling studies using [(3)H]uridine showed a strongly decreased biosynthesis of CTP via CTP synthetase. Retinoic acid likely confers resistance of neuroblastoma cells to CPEC in part by slowing down proliferation, and in part by shifting the synthesis of CTP towards the salvage of cytidine, thereby bypassing CTP synthetase. |
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Authors:
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Jörgen Bierau; Albert H van Gennip; René Leen; Huib N Caron; André B P van Kuilenburg |
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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: FEBS letters Volume: 527 ISSN: 0014-5793 ISO Abbreviation: FEBS Lett. Publication Date: 2002 Sep |
Date Detail:
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Created Date: 2002-09-10 Completed Date: 2002-11-08 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0155157 Medline TA: FEBS Lett Country: Netherlands |
Other Details:
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Languages: eng Pagination: 229-33 Citation Subset: IM |
Affiliation:
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Academic Medical Center, University of Amsterdam, Department of Clinical Chemistry and Emma Children's Hospital, P.O. Box 22700, 1100 DE, Amsterdam, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology* Apoptosis / drug effects Cell Differentiation / drug effects Cell Division / drug effects Cytidine / analogs & derivatives*, pharmacology* Cytidine Triphosphate / biosynthesis Drug Interactions Humans Neuroblastoma / drug therapy*, metabolism, pathology Polyphosphates / metabolism Tretinoin / pharmacology* Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Polyphosphates; 10380-08-2/triphosphoric acid; 302-79-4/Tretinoin; 65-46-3/Cytidine; 65-47-4/Cytidine Triphosphate; 90597-22-1/cyclopentenyl cytosine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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