Abstract
AbstractTel03 (N,N′‐Bis‐(2‐(dimethylamino)ethyl)‐3,4,9,10‐perylentetra‐carboxylic acid diimide), a perylene derivative, was synthesized and its interaction with different forms of human telomeric DNA examined . The effect of Tel03 on leukemia cells in short‐term cultures was also used to explore its molecular actions. Electrospray ionization mass spectrometry (ESI‐MS) analysis indicated that Tel03 specifically recognizes telomeric quadruplex, not duplex DNA. After the treatment with Tel03 (0.1–10 µM) for 48 h, telomerase activity in K562 leukemia cell extracts was inhibited in a dose‐dependent manner as assessed with a telomere repeat amplification protocol (TRAP) assay. MTT assay results showed that Tel03 (0.1–10 µM) inhibited the proliferation of K562 cells after treatment for 72 h. In addition, apoptosis was observed. Using real‐time quantitative PCR and Western blot analysis, the expression of c‐myc and bcl‐2 was markedly down‐regulated at both the mRNA and protein levels. However, no changes were observed in the expression of bax. We conclude that G‐quadruplex ligand, Tel03, is a novel telomerase inhibitor and apoptosis‐inducing agent in leukemia cells acting via down‐regulation of bcl‐2 and c‐myc. Tel03 has the potential to be developed as an antileukemia drug. Drug Dev Res 69:235–241, 2008. © 2008 Wiley‐Liss, Inc.
Published Version
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