Time-Dependent Inhibitory Effect of Non-Nucleosidic Telomerase Inhibitor on NB4 Cell Proliferation through Transcriptional Suppression of Catalytic Subunit

Since stimulated telomerase activity provides nearly all of human malignancies including acute promyelocytic leukemia (APL) with unlimited proliferative potential، targeting telomerase seems to be an effective approach in cancer treatment. In this regard، BIBR1532، a small-molecule inhibitor of telomerase، has been shown to increase the therapeutic window of current chemotherapeutic regimens. This study was aimed to investigate the effects of BIBR1532 on cell proliferation as well as transcriptional alteration of hTERT (the catalytic subunit of telomerase). NB4 leukemic cells were treated with various concentrations of BIBR1532 and succeeding trypan blue exclusion assay، BrdU cell proliferation assay، and quantitative real-time PCR were applied to investigate cell viability index، cell proliferation and time-dependent alteration of hTERT mRNA levels. BIBR1532 decreased cell viability index and exerted an antiproliferative effect against NB4 leukemic cells; we found that exposing cells with BIBR1532 at 30، 60 and 90 μM for 72 h inhibited DNA synthesis rate by 24، 45 and 70%، respectively. Furthermore، transcriptional suppression of hTERT was found upon NB4 treatment by BIBR1532 in a time- and dose-dependent manner. Based on the short telomere length and high terlomerase activity in APL as well as antiproliferative effect of BIBR1532 against NB4 cells، anti-telomerase-based therapy might be regarded as a successful strategy in APL therapy.