Interference with telomerase and telomere maintenance is emerging as an 
attractive target for anticancer therapies. Ligand-induced stabilization of 
G-quadruplex formation by the telomeric DNA 3'-overhang inhibits telomerase from 
catalyzing telomeric DNA synthesis and from capping telomeric ends, making these 
ligands good candidates for chemotherapeutic purposes. BRACO-19 is one of the 
most effective and specific ligand for telomeric G4. It is shown here that 
BRACO-19 suppresses proliferation and reduces telomerase activity in human 
glioblastoma cells, paralleled by the displacement of telomerase from nuclear to 
cytoplasm. Meanwhile, BRACO-19 triggers extensive DNA damage response at 
telomere, which may result from uncapping and disassembly of telomeric T-loop 
structure, characterized by the formation of anaphase bridge and telomere 
fusion, as well as the release of telomere-binding protein from telomere. The 
resulting dysfunctional telomere ultimately provokes p53 and p21-mediated cell 
cycle arrest, apoptosis and senescence. Notably, normal primary astrocytes do 
not respond to the treatment of BRACO-19, suggesting the agent's good 
selectivity for cancer cells. These results reinforce the notion that 
G-quadruplex binding compounds can act as broad inhibitors of telomere-related 
processes and have potential as selective antineoplastic drugs for various 
tumors including malignant gliomas.