Cell senescence and telomere shortening induced by a new series of specific G-quadruplex DNA ligands.

摘要: Telomeres of human chromosomes contain a G-rich 3′-overhang that adopts an intramolecular G-quadruplex structure in vitro which blocks the catalytic reaction telomerase. Agents stabilize G-quadruplexes have potential to interfere with telomere replication by blocking elongation step catalyzed telomerase and can therefore act as antitumor agents. We identified Fluorescence Resonance Energy Transfer new series quinoline-based ligands also exhibit potent specific anti-telomerase activity IC50 nanomolar concentration range. Long term treatment tumor cells at subapoptotic dosage induces delayed growth arrest depends on initial length. This is associated erosion appearance senescent cell phenotype (large size expression β-galactosidase activity). Our data show interacting agent able impair function thus providing basis for development anticancer