TELOMESTATIN

Telomestatin (0-50 μM) promotes or stabilizes the formation of the intramolecular G-quadruplex. At the DNA concentrations of 0.005 and 0.2 µM, EC ₅₀ values of 0.03 µM and 0.53 µM telomestatin are found. In a parallel experiment with the mutated oligonucleotide d[T2AGAG]4, there is no conversion of the mutated sequence to a G-quadruplex structure by telomestatin.Telomestatin (2-10 μM) effects the expression of DN-hTERT on telomerase activity and telomere length, at 10 μM，the expression of DN-hTERT shows a significant reduction of telomerase activity. Additionally, at 2 μM , the terminal restriction fragment (TRF) length of U937 cells shortens progressively from 9.5 to 3.8 kb at population doubling (PD) 20 in U937 cells.Telomestatin (2-5 μM; short-time or long trem) has less effect on normal diploid human fibroblasts and ALT-positive cells.Telomestatin (5 μM; short-time 3 days) exposure has no affect the viability of normal human fibroblasts BJ or IMR-90; however, 5 μM of telomestatin reduces the viability of GM847 cells.Telomestatin (2 μM; long-term 10-50 days) does not significantly change the proliferation rate or viability to that of control cells in BJ or IMR-90 cells and also does not change the proliferation of GM847 cells.

Telomestatin (intraperitoneal injection; 3-15 mg/kg; two times a week; 4 weeks) decreases tumor telomerase activity and inhibits the growth of U937 xenografts. Systemic administrations of 3 mg/kg or 9 mg/kg or 15 mg/kg of telomestatin decreases tumor telomerase activity by 60.2%, 74% and 92.5% compared to control, respectively.