Journal of Iranian Blood Transfusion

Abstract

Background and Objectives

As the role of telomerase in unlimited proliferation is a common feature of the majority of human cancers including hematological malignancies, thus inhibition of this enzyme has been proposed as a novel strategy in cancer therapeutics. This study was performed to investigate the effect of BIBR1532, a synthetic inhibitor of hTERT, on metabolic activity, DNA synthesis rate, cell cycle activity, and expression of pro-apoptotic genes such as p21, p73, Bax, and Bad in Nalm-6 pre-B ALL cells.

Materials and Methods

In  an experimental study, to investigate the effect of BIBR1532, Nalm-6 leukemic cells were cultured in the presence of various concentrations of the inhibitor and consequently MTT assay, BrdU cell proliferation assay, flowcytometeric cell cycle analysis, and quantitative real-time PCR were applied.

Results

Our results revealed that BIBR1532 induces an inhibitory effect on metabolic activity and DNA synthesis rate of Nalm-6 cells in a dose- and time-dependent manner. Moreover, we found that BIBR1532 exerts an inductive effect on mRNA expression level of Bax, Bad, p73, and p21, which in turn leads to G₁ cell cycle arrest and increased sub-G₁ cell population.

Conclusions

Since treatment with BIBR1532 could arrest the cell cycle activity in Nalm-6 cells and activate cellular apoptotic pathway, anti-telomerase-based therapy may be regarded as a novel promising strategy for ALL treatment.