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Background: To date, several drugs have been proposed for the treatment of acute promyelocytic leukemia (APL) however, none of them has resulted in complete remission. Therefore, many efforts are in progress to find new drugs with the capability of inducing apoptosis. Recently, anti-carcinogenic effects have been reported for a drug named carbenoxolone (CBX) on several cell lines. In the present study, the effects of CBX on NB4 cell line, as an experimental model of APL, were examined. Materials and Methods: In this trial, NB4 cell line was cultured and treated with different concentrations of CBX (50-250µM) in various time intervals (12-48 hours). Trypan blue exclusion test was used to evaluate growth inhibitory and viability effects of the drug on NB4 cell line. Fluorescent microscopy (acridine orange/ethidium bromide double-staining) and agarose gel electrophoresis DNA were used to study apoptosis. Results: CBX induced growth inhibition of NB4 cells so that growth inhibition rates of NB4 cells, after the 48 hour of treatment with 50, 100, 150, 200, and 250 µM CBX were 32.65, 47.52, 60.73, 68.91, and 74.33%, respectively. Furthermore, the results of DNA fragmentation and fluorescent microscopy assays indicated that apoptosis is a major mode of cell death after treatment of NB4 cells with above concentrations of CBX. Conclusion: Noticing the growth inhibitory and apoptotic effects of CBX on human promyelocytic leukemia NB4 cells, it can be considered as a potential candidate for further studies on APL treatment.

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Background: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.