The effect of telomerase inhibitor MST-312 on apoptosis of acute lymphoblastic leukemia cell line NALM-6
Journal Title: Khoon - Year 2018, Vol 15, Issue 2
Abstract
The effect of telomerase inhibitor MST-312 on apoptosis of acute lymphoblastic leukemia cell line NALM-6 Ghasemimehr N.1, Yazdani Z.1, Farsinejad A.R.1, Mirzaee Khalilabadi R.1, Fatemi A.1 1Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Kerman University of Medical Sciences, Kerman, Iran Abstract Background and Objectives There have been continuous efforts in telomerase-targeted therapy for cancer treatment because telomerase expression is significantly increased in about 85- 90% of human cancers while its expression is usually silenced in normal cells. Materials and Methods Throughout this experimental study, NALM-6 cells were treated with different concentrations of telomerase inhibitor, MST-312 at different times. Then, cell viability and metabolic activity were evaluated by trypan blue and MTT assays; cell apoptosis was also evaluated by flow cytometry using Annexin V Apoptosis Detection Kit. In addition, the expression of BAX and BCL2 genes was evaluated in the treated cells using Quantitative Real-time PCR. Results A dose-and time-dependent decrease was observed in the viability of NALM-6 cells after exposure with different concentration of MST-312. Over 50% decrease was observed in the viability of the cells treated with 8 μM of MST-312 after 48 h. The cytotoxic effect of MST-312 was dose- dependent, with approximately 6, 19.69 and 56.9% reduction in metabolic activity of NALM-6 cells after 48 h exposure with 2, 4, and 8 μM of MST-312, respectively. Approximately 20% apoptosis was observed in NALM-6 cells treated with 4μM of MST-312 after 48 h. Gene expression analysis also showed that 4μM of MST-312 led to upregulation of BAX and downregulation of Bcl-2 genes. Conclusions Inhibition of telomerase activity by MST-312 can be proposed as a new candidate for the treatment of acute lymphoblastic leukemia. Key words: Telomerase, Apoptosis, Acute Lymphoid Leukemia Received: 8 Apr 2018 Accepted: 9 May 2018 Correspondence: Fatemi A., PhD of Hematology & Blood Banking. Assistant Professor of Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Kerman University of Medical Sciences. Postal Code: 7619794435, Kerman, Iran. Tel: (+9834) 32112007; Fax: (+9834) 31325375 E-mail: ahmad.fatemi2@gmail.com
Authors and Affiliations
N. Ghasemimehr, Z. Yazdani, A. R. Farsinejad, R. Mirzaee Khalilabadi, A. Fatemi
Keywords
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