Induction of cell death and apoptosis in NB4 promyelocytic leukemic cells using Oligonucleotide as a telomerase antagonist

Acute promyelocytic leukemia (APL) is characterized by a specific t(15;17), distinct morphologic picture, and a clinical coagulopathy that contributes to the morbidity and mortality of the disease. Telomerase is consistently activated in nearly all APL patients and telomerase-mediated telomere stabilization is responsible for unlimited replicative potential of the disease. This study aimed to investigate the effects of designed oligonucleotide as a telomerase inhibitor on NB4 cells.
NB4 leukemic cells were treated with various concentrations of oligonucleotide by transfection method using lipofectamin 2000. The inhibitory effect of oligonucleotide on cell metabolic activity and cell viability was assessed by MTT assay. Quantitative real-time PCR were applied to investigate alteration of Bax and Bcl-2 mRNA levels.
Oligonucleotide decreased cell viability index and exerted cytotoxic effect against NB4 leukemic cells; we found that exposing cells with Oligonucleotide at 40 pMol for 48 h induced cell death and apoptotic effects on NB4 cells. Furthermore, transcriptional suppression of Bcl-2 and upregulation of Bax were found upon NB4 treatment by oligonucleotide.
Based on the short telomere length and high terlomerase activity in APL as well as inhibitory effect of oligonucleotide against NB4 cells, anti-telomerase-based therapy might be regarded as a successful strategy in APL therapy.