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Ghanizadeh-Vesali S, Shirali S, Zaker F, Mohammadi S, Aryanpour J, Yazdanparast S. Simvastatin synergistically potentiating the anti-tumoreffects of arsenic trioxide on human promyelocyticleukemia (NB-4) cells. bloodj 2014; 11 (2) :116-125
URL: http://bloodjournal.ir/article-1-732-en.html
Simvastatin synergistically potentiating the anti-tumoreffects of arsenic trioxide on human promyelocyticleukemia (NB-4) cells
S. Ghanizadeh-Vesali , S. Shirali , Farhad Zaker * , S. Mohammadi , J. Aryanpour , S.A. Yazdanparast
Keywords: Key words: Acute Promyelocytic Leukemia, arsenic trioxide, Simvastatin, Apoptosis
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Sci J Iran Blood Transfus Organ 2014; 11(2): 116-125
 
Original Article
 
 

Simvastatin synergistically potentiating the anti-tumor
effects of arsenic trioxide on human promyelocytic
leukemia (NB-4) cells
 
Ghanizadeh-Vesali S.1, Shirali S.2, Zaker F.1, Mohammadi S.3, Aryanpour J.1,
Yazdanparast S.A.4
 
 
1School of Allied Medicine, Cellular Molecular Research Center of Iran University of Medical Sciences, Tehran, Iran.
2School of Allied Medicine, Jundishapur University of Medical Sciences, Ahvaz, Iran.
3School of Allied Medicine, Islamic Azad University-Tehran Medical Branch, Tehran, Iran.
4School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.
 
Abstract
Background and Objectives
The efficacy of arsenic trioxide (ATO), as a poisonous drug, in the treatment of acute promyelocytic leukemia (APL) is widely accepted. Due to adverse effects associated with high-dose ATO, the combination therapy is a rational therapeutic strategy to enhance the effectiveness of ATO. In this regard, we used simvastatin (SV), a cholesterol lowering medication, and hypothesized that SV plus ATO would potentiate the efficacy of ATO at lower doses.
 
Materials and Methods
To evaluate the effects of SV and ATO treatment (in isolation or in combination) on transcriptional levels of Bax and Bcl-2, apoptosis, growth kinetic, and metabolic activity of NB-4 cells, we employed RQ-PCR, flowcytometry, trypan blue dye exclusion, and MTT assays, respectively. The data were analyzed using SPSS 21, student’s t-test and one-way ANOVA tests.
 
Results
Both SV and ATO considerably hindered the metabolic activity of NB-4 cells in a concentration-dependent manner. In addition, the co-treatment with them exerted an indicative decline in viability, and a significant augmentation in apoptotic population and in the ratio of Bax to Bcl-2 mRNA level.
 
Conclusions 
Our results have demonstrated that ATO and SV cooperate synergistically to induce cell death and to inhibit the proliferation rate of NB-4 cells. Furthermore, our results suggest that the combination treatment increased the programmed cell death rate probably through enhancing the intrinsic mitochondrial apoptotic pathway. On aggregate and in view of these data, SV showed the potency for attenuating the effective dose of ATO.
 
Key words: Acute Promyelocytic Leukemia, arsenic trioxide, Simvastatin, Apoptosis
 
Received: 11 Mar 2013
Accepted:  8 Oct  2013
 
 

Correspondence: Zaker F., PhD of Hematology. Professor of School of Allied Medicine, Cellular Molecular Research Center of Iran University of Medical Sciences.
P.O.Box: 14155-6183, Tehran, Iran. Tel: (+9821) 88622576; Fax: (+9821) 88622576
E-mail:
farhadz20@yahoo.co.uk
Type of Study: Research | Subject: Hematology
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