Pro-apoptotic effect of BIBR1532 on APL cell line: Induction of rapid cell death independent of progressive shortening of telomere length

Since nearly 90% of patients with acute promyelocytic leukemia (APL) have high telomerase activity and significant shortened telomere length، these patients have، therefore، been suggested to be good candidates for the therapeutic intervention with telomerase inhibitors. This study was done to investigate the effects of BIBR1532، a non-nucleoside inhibitor of telomerase، on APL cells.

In this experimental study، for investigating the effect of BIBR1532، NB4 leukemic cells were cultured in the presence of various concentrations of BIBR1532. Succeeding apoptosis assay، Caspase-3 activity assay، and quantitative real-time PCR were applied to examine the effect of this drug on apoptosis percenage، enzymatic activity of Caspase-3، and quantitative expression of genes mRNA involved in apoptosis.

The results showed that BIBR1532 induced apoptosis in NB4 cells in a dose-dependent maner. Moreover، real time PCR results showed that BIBR1532 led to a significant decrease in mRNA of Bcl-2 gene and signficant increases in transcription of Bax، PUMA، and Caspase-3.

Since treatment with BIBR1532 could exert rapid apoptotic cell death in NB4 cells andactivate cellular apoptosis route، anti-telomerase-based therapy can regarded as a suitable strategy for APL treatment. Patients with progressive shortening of telomere length and high levels of telomerase activity are suitable candidates for treatment with telomerase inhibitors.