Agents stabilizing G-quadruplexes have the potential to interfere with telomere replication by blocking the elongation step catalysed by
telomerase or
telomerase-independent mechanism and could therefore act as
antitumor agents. In this study, we found that
quindoline derivatives interacted preferentially with intramolecular G-quadruplex structures and were novel potent
telomerase inhibitors. Treatment with
quindoline derivatives reproducibly inhibited
telomerase activity in human
leukemia K562 cells and
colon cancer SW620 cells. N'-(10H-Indolo [3,2-b] quinolin-11-yl)-N, N-dimethyl-propane-1,3-diamine (SYUIQ-5), (one of
quindoline derivatives), when added to K562 and SW620 cell culture at nonacute cytotoxic concentrations, increased time of population doublings of K562 and SW620 cells, induced a marked cessation in cell growth and cellular senescence phenotype after 35 and 18 days, respectively. Growth cessation was accompanied by a shortening of telomere length, and induction of p16, p21 and p27
protein expression. However, another compound SYUIQ-7 with greater IC(50) for
telomerase had no obvious cellular effect in nonacute cytotoxic concentrations. These results indicate that
quindoline derivatives as novel potent G-quadruplex interactive agents induce senescence and telomere shortening in
cancer cells and therefore are promising agents for
cancer treatment.