G-quadruplex (G4) is a higher-order nucleic acid structure that is formed by 
guanine-rich sequences. G4 stabilization by small-molecule compounds called G4 
ligands often causes cytotoxicity, although the potential medicinal impact of 
this effect has not been fully established. Here we demonstrate that a synthetic 
G4 ligand, Y2H2-6M(4)-oxazole telomestatin derivative (6OTD), limits the growth 
of intractable glioblastoma (grade IV glioma) and glioma stem cells (GSCs). 
Experiments involving a human cancer cell line panel and mouse xenografts 
revealed that 6OTD exhibits antitumor activity against glioblastoma. 6OTD 
inhibited the growth of GSCs more potently than it did the growth of 
differentiated non-stem glioma cells (NSGCs). 6OTD caused DNA damage, G1 cell 
cycle arrest, and apoptosis in GSCs but not in NSGCs. These DNA damage foci 
tended to colocalize with telomeres, which contain repetitive G4-forming 
sequences. Compared with temozolomide, a clinical DNA-alkylating agent against 
glioma, 6OTD required lower concentrations to exert anti-cancer effects and 
preferentially affected GSCs and telomeres. 6OTD suppressed the intracranial 
growth of GSC-derived tumors in a mouse xenograft model. These observations 
indicate that 6OTD targets GSCs through G4 stabilization and promotion of DNA 
damage responses. Therefore, G4s are promising therapeutic targets for 
glioblastoma.