Document Detail


Alternative responses of primary tumor cells and glioblastoma cell lines to N,N-bis-(8-hydroxyquinoline-5-yl methyl)-benzyl substituted amines: cell death versus P53-independent senescence.
MedLine Citation:
PMID:  21042714     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
N,N-bis-(8-hydroxyquinoline-5-yl methyl)-benzyl substituted amines (HQNBA) represent a new class of compounds showing anti-cancer activity. At the chemical level the compounds were shown to react preferentially with thiol radicals which may lead to unfolded cysteine containing proteins and subsequent ER-stress. At the molecular level, treatment of U87 cells with this class of derivatives induced an over-expression of stress genes, including P53 and numerous P53 target genes. By generating shRNA U87 cell clones impaired in P53 expression we found that P53 mediates neither proliferation arrest of treated U87 cells nor over-expression of potential P53 targets. Moreover, we discovered that a representative HQNBA derivative (JLK1486) induces strong but transient senescence in U87 cells in a P53-independent manner. We demonstrate that, in contrast to its effect on established glioblastoma cell lines, JLK1486 induces extensive death of primary glioblastoma cells. We provide evidence that both caspase 3, and 7 activation, and cathepsin B and D activities account for at least part of this cell death.
Authors:
Jean-Louis Kraus; Filippo Conti; Sébastien Madonna; Aurelie Tchoghandjian; Christophe Beclin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of oncology     Volume:  37     ISSN:  1791-2423     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-02     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1463-70     Citation Subset:  IM    
Affiliation:
CNRS, IBDML-UMR-6216, Campus de Luminy Case 907, 13288 Marseille cedex 09, France.
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