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Asghari kia L, Bashash D, Ghaffari S, Hamid poor M, Ghavamzadeh A. Induction of cell death and apoptosis in NB4 promyelocytic leukemic cells using Oligonucleotide as a telomerase antagonist . Sci J Iran Blood Transfus Organ 2016; 13 (1) :1-10
URL: http://bloodjournal.ir/article-1-949-en.html
Induction of cell death and apoptosis in NB4 promyelocytic leukemic cells using Oligonucleotide as a telomerase antagonist
L. Asghari kia , D. Bashash , S.H. Ghaffari * , M. Hamid poor , A. Ghavamzadeh
Keywords: Key words: Acute Promyelocytic Leukemia, Apoptosis, Cell Death
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Sci J Iran Blood Transfus Organ 2016; 13(1): 1-10
 
Original  Article
 
 

Induction of cell death and apoptosis in NB4
promyelocytic leukemic cells using Oligonucleotide
as a telomerase antagonist
 
Asghari Kia L.1, Bashash D.1, Ghaffari S.H.2, Hamidpour M.3, Ghavamzadeh A.2
 
 
1Department of Hematology, Faculty of Allied Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2Hematology, Oncology and Stem Cell Research Center of Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
3Faculty of Allied Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
 
Abstract
Background and Objectives
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.
 
Materials and Methods
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.
 
Results
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.
 
Conclusions
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.
 
Key words: Acute Promyelocytic Leukemia, Apoptosis, Cell Death
 
 
 
 
 
 
Received:  18 Mar 2015
Accepted: 28 Oct  2015
 
 
 
 

Correspondence: Ghaffari SH., PhD of Molecular Genetics. Associate Professor of Hematology, Oncology and Stem Cell Research Center, Tehran University of Medical Sciences, Shariati Hospital, Kargar Street.
Postal code: 14111, Tehran, Iran. Tel: (+9821) 84902665; Fax: (+9821) 88004140
E-mail: shghaffari@tums.ac.ir
Type of Study: Research | Subject: Hematology
Published: 2016/03/12
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