Document Detail


Inhibition of choline kinase as a specific cytotoxic strategy in oncogene-transformed cells.
MedLine Citation:
PMID:  14654777     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cancer treatment is in the need of selective drugs that can interfere specifically with signalling pathways affected during the carcinogenic process. Identification of new potential molecular targets is the key event in the design of new anticancer strategies. Once identified, attempts for the generation of specific molecules to regulate their function can be achieved. The relevance of deregulation of choline kinase (ChoK, E.C. 2.7.1.32) in oncogene-driven cell transformation has been previously demonstrated. Here we provide strong evidence that MN58b, a selective inhibitor of ChoK, is rather specific to this enzyme, with no effect on a variety of oncogene-activated signalling pathways involved in the regulation of cell proliferation. MN58b does not affect MAPKs, PI3K, and other enzymes involved in the regulation of phospholipid metabolism such as phospholipases C, D, and A2, CTP:phosphocholine cytidylyltransferase, or diacylglycerol choline-phosphotransferase. Consistent with this specificity, ectopic expression of ChoK resulted in resistance to its inhibitor. Finally, nontransformed cells were able to resume cell proliferation after removal of the drug, while transformed cells were irreversibly affected. These results indicate that inhibition of ChoK is a rather specific strategy for the cytotoxic treatment of transformed cells.
Authors:
Agustín Rodríguez-González; Ana Ramírez de Molina; Félix Fernández; Maria Angeles Ramos; Maria del Carmen Núñez; Joaquín Campos; Juan Carlos Lacal
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncogene     Volume:  22     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2003-12-05     Completed Date:  2004-01-09     Revised Date:  2007-09-25    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  8803-12     Citation Subset:  IM    
Affiliation:
Department of Molecular and Cellular Biology of Cancer, Instituto de Investigaciones Biomédicas (CSIC), Arturo Duperier 4, Madrid 28029, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / pharmacology*
Cell Division / drug effects*
Cell Transformation, Neoplastic
Choline Kinase / antagonists & inhibitors*
Hemicholinium 3 / analogs & derivatives*
Mice
NIH 3T3 Cells
Neoplasms / drug therapy*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 312-45-8/Hemicholinium 3; EC 2.7.1.32/Choline Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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