Volume 10, Issue 2 (Summer 2013)                   Sci J Iran Blood Transfus Organ 2013, 10(2): 129-139 | Back to browse issues page

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Hasani S, Zaker F, Zekri A, Zaghal A, Alimoghaddam K, Ghavamzadeh A et al . Apoptotic effect of arsenic trioxide plus Azidothymidine on APL cell line (NB4) through P21 expression and cell cycle distribution changes . Sci J Iran Blood Transfus Organ 2013; 10 (2) :129-139
URL: http://bloodjournal.ir/article-1-769-en.html
Apoptotic effect of arsenic trioxide plus Azidothymidine on APL cell line (NB4) through P21 expression and cell cycle distribution changes
S. Hasani , F. Zaker , A. Zekri , A. Zaghal , K. Alimoghaddam , A. Ghavamzadeh , S.H. Ghaffari *
Keywords: Key words: Acute Promyelocytic Leukemia, arsenic trioxide, Azidothymidine, Apoptosis
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Original Article
 
 
 
 
Sci J Iran Blood Transfus Organ 2013; 10(2): 129-139
 
 
 
 
 
 


Apoptotic effect of arsenic trioxide plus Azidothymidine
 on APL cell line (NB4) through P21 expression
and cell cycle distribution changes
 
Hassani S.1, Zaker F.1, Zekri A.2, Zaghal A.3, Alimoghaddam A.3,
Ghavamzadeh A.3, Ghaffari S.H.3
 
 
1School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
2School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
3Hematology, Oncology and Stem Cell Research Center of Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
 
Abstract
Background and Objectives
Arsenic trioxide (ATO) is an active drug in treatment of acute promyelocytic leukemia (APL), but has adverse effects on patients. In order to enhance antileukemic effectiveness and to reduce dosage of ATO, combinatorial effect of it with Azidothymidine (AZT) in apoptosis induction was evaluated on APL cell line (NB4).
 
Materials and Methods
The cells cultured and treated with 50 μM AZT and/or ATO for 48 hrs and then with apoptosis, cell cycle distribution, and P21 mRNA levels in comparison with untreated cells (control) were analyzed by flow cytometry and Real Time PCR, respectively.
 
Results
ATO led to induction of apoptosis (50.14% ± 7.12) in comparison with the control (3.9% ± 2.97) through the increment of the cell cycle arrest in G2/M. The apoptotic effect of ATO had been inhibited in cells treated with combination of AZT/ATO (24.35% ± 4.65). This inhibition was associated with the relative reduction of the cells in G2/M and relative increase of the cells in G1 phase. While ATO had suppressive effect on p21 gene expression (0.27±0.14), AZT (1.81 ± 0.21) and AZT/ATO (2.06 ± 0.32) induced it.
 
Conclusions 
AZT attenuates ATO-caused apoptosis possibly through the induction of p21 expression and subsequent relative evasion from G2/M arrest and accumulation of cells in G1 phase.
 
Key words: Acute Promyelocytic Leukemia, arsenic trioxide, Azidothymidine, Apoptosis
 
 
 
 
 
 
Received: 30 May 2012
Accepted:  7 Oct  2012
 
 
 

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: 2013/08/24
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