Document Detail


MDDD, a 4,9-diazapyrenium derivative, is selectively toxic to glioma cells by inducing growth arrest at G0/G1 independently of p53.
MedLine Citation:
PMID:  16633716     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
4-Methyl-2,7-diamino-5,10-diphenyl-4,9-diaz-apyrenium chloride (MDDD), a stable and water soluble nucleic acid-intercalating agent, was shown to be toxic to cancer cells with IC50 around 10 microM. IC(50) We tested MDDD for its potential antitumor activities and found it inhibited cancer cell growth with IC(50) in the micromolar range for the majority of cancer cells tested, with the exception of glioma cells, for which the IC(50) is in the submicromolar range. This unique selectivity of MDDD to glioma cells can potentially be exploited for anti-glioma therapeutics. Although the underlying mechanisms for the apparent glioma specificity remain to be elucidated, our analysis indicates that MDDD significantly reduces cell clonogenicity and blockes cell proliferation at the G1 phase. MDDD treatment also triggers induction of p53 and p21 at the protein levels, suggesting the activation of DNA damage response. However, MDDD mediated growth inhibition does not require the p53 pathway since p53+/- isogenic cell pairs display the same sensitivity. These properties of MDDD favor its candidacy for evaluation as a new anti-tumor agent, particularly for glioma.
Authors:
De-Hua Yu; James Macdonald; Steve Josephs; Qi Liu; Vivian Nguy; Yitzhak Tor; Flossie Wong-Staal; Qi-Xiang Li
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Investigational new drugs     Volume:  24     ISSN:  0167-6997     ISO Abbreviation:  Invest New Drugs     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-08-22     Completed Date:  2007-10-11     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8309330     Medline TA:  Invest New Drugs     Country:  United States    
Other Details:
Languages:  eng     Pagination:  489-98     Citation Subset:  IM    
Affiliation:
Immusol Inc., 10790 Roselle Street, San Diego, CA 92121, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / pharmacology*
Apoptosis
Cell Cycle / drug effects*
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
DNA / drug effects,  metabolism
DNA Damage
G0 Phase
G1 Phase
Glioma / genetics,  metabolism,  pathology*
Humans
Inhibitory Concentration 50
Intercalating Agents / pharmacology*
Neoplastic Stem Cells / drug effects
Pyridinium Compounds / pharmacology*
RNA Interference
Rats
Tumor Stem Cell Assay
Tumor Suppressor Protein p53 / genetics,  metabolism
Chemical
Reg. No./Substance:
0/4-methyl-2,7-diamino-5,10-diphenyl-4,9-diaz-apyrenium chloride; 0/Antineoplastic Agents; 0/Intercalating Agents; 0/Pyridinium Compounds; 0/Tumor Suppressor Protein p53; 9007-49-2/DNA

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


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