| MDDD, a 4,9-diazapyrenium derivative, is selectively toxic to glioma cells by inducing growth arrest at G0/G1 independently of p53. | |
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MedLine Citation:
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PMID: 16633716 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article |
Journal Detail:
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Title: Investigational new drugs Volume: 24 ISSN: 0167-6997 ISO Abbreviation: Invest New Drugs Publication Date: 2006 Nov |
Date Detail:
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Created Date: 2006-08-22 Completed Date: 2007-10-11 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8309330 Medline TA: Invest New Drugs Country: United States |
Other Details:
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Languages: eng Pagination: 489-98 Citation Subset: IM |
Affiliation:
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Immusol Inc., 10790 Roselle Street, San Diego, CA 92121, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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