MDDD, a 4,9-diazapyrenium derivative, is selectively toxic to glioma cells by inducing growth arrest at G0/G1 independently of p53.

Investigational New Drugs
De-Hua YuQi-Xiang Li

Abstract

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.

References

Aug 1, 1987·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·T W PendergrassW A Bleyer
Mar 29, 2000·CA: a Cancer Journal for Clinicians·R T GreenleeP A Wingo
Sep 21, 2002·Cancer Cell·Thijn R BrummelkampReuven Agami
Jan 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·Gustavo TiscorniaInder M Verma
Sep 4, 2003·The Cancer Journal·Ian F Parney, Susan M Chang
May 4, 2004·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·H H FiebigA M Burger
May 22, 2004·BioTechniques·Ning KeQi-Xiang Li
Jul 29, 2004·DNA Repair·Yinhuai Chen, Yolanda Sanchez

❮ Previous
Next ❯

Citations

Nov 24, 2007·Cancer Chemotherapy and Pharmacology·Saska MarcziMladen Zinić
Aug 25, 2020·Chemistry of Heterocyclic Compounds·Andrey M ZhirovIvan V Borovlev
Aug 4, 2009·Journal of Agricultural and Food Chemistry·Li-Ching ChenWen-Sen Lee

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.