| Evaluation of Polo-like Kinase 1 inhibition on the G2/M checkpoint in Acute Myelocytic Leukaemia. | |
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MedLine Citation:
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PMID: 18616938 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Polo-Kinase 1 (PLK1) is a key cell cycle regulator that is necessary for checkpoint recovery after DNA damage-induced G2 arrest. We have examined the effects of PLK inhibition in Acute Myelocytic Leukaemia (AML) cells, whose resistance to genotoxic agents is thought to be associated with checkpoint reinforcement. We report that in U937 AML cells, PLK1 participates in checkpoint recovery, and that inhibition of PLK by the GW843682X compound results in mitotic accumulation and apoptosis. We also found that when challenged with VP-16, inhibition of PLK1 prevented U937 cells from checkpoint exit. Finally, we found that treatment with GW843682X slightly reduced genotoxic-induced inhibition of colony formation efficiency of primary leukaemia cells (CFU-L) from AML patients. |
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Authors:
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Christine Didier; Cindy Cavelier; Muriel Quaranta; Cécile Demur; Bernard Ducommun |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-06-19 |
Journal Detail:
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Title: European journal of pharmacology Volume: 591 ISSN: 0014-2999 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2008 Sep |
Date Detail:
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Created Date: 2008-08-12 Completed Date: 2008-10-15 Revised Date: 2011-11-02 |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 102-5 Citation Subset: IM |
Affiliation:
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Institut d'Exploration Fonctionnelle des Génomes, University of Toulouse, 118 route de Narbonne, 31062 Toulouse, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents, Phytogenic
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pharmacology Benzimidazoles / pharmacology* Cell Cycle Proteins / antagonists & inhibitors*, metabolism Cell Division / drug effects Etoposide / pharmacology G2 Phase / drug effects Humans Leukemia, Myeloid, Acute / metabolism* Mitosis / drug effects Protein-Serine-Threonine Kinases / antagonists & inhibitors*, metabolism Proto-Oncogene Proteins / antagonists & inhibitors*, metabolism Thiophenes / pharmacology* U937 Cells |
| Chemical | |
Reg. No./Substance:
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0/5-(5,6-dimethoxy-1H-benzimidazol-1-yl)-3-((2-(trifluoromethyl)benzyl)oxy)thiophene-2-carboxamide; 0/Antineoplastic Agents, Phytogenic; 0/Benzimidazoles; 0/Cell Cycle Proteins; 0/Proto-Oncogene Proteins; 0/Thiophenes; 33419-42-0/Etoposide; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/polo-like kinase 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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