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Induction of G1 Cell Cycle Arrest and Increased Sub-G1 Population upon Treatment of Nalm-6 Cells with Synthetic Inhibitor of hTERT
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M. Zarei   , D. Bashash |
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| Keywords: Key words: Acute Lymphoid Leukemia, BIBR1532, Telomerase |
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Full-Text [PDF 527 kb]
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Type of Study: Research |
Subject:
Hematology
Published: 2016/12/25
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Full-Text: (6236 Views) |
References :
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Sci J Iran Blood Transfus Organ 2017; 13(4): 314-323
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Induction of G1 Cell Cycle Arrest and Increased Sub-G1 Population upon Treatment of Nalm-6 Cells with Synthetic Inhibitor of hTERT
Zareii M.1, Bashash D.1
1Hematology Department, Faculty of Allied Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract
Background and Objectives
As the role of telomerase in unlimited proliferation is a common feature of the majority of human cancers including hematological malignancies, thus inhibition of this enzyme has been proposed as a novel strategy in cancer therapeutics. This study was performed to investigate the effect of BIBR1532, a synthetic inhibitor of hTERT, on metabolic activity, DNA synthesis rate, cell cycle activity, and expression of pro-apoptotic genes such as p21, p73, Bax, and Bad in Nalm-6 pre-B ALL cells.
Materials and Methods
In an experimental study, to investigate the effect of BIBR1532, Nalm-6 leukemic cells were cultured in the presence of various concentrations of the inhibitor and consequently MTT assay, BrdU cell proliferation assay, flowcytometeric cell cycle analysis, and quantitative real-time PCR were applied.
Results
Our results revealed that BIBR1532 induces an inhibitory effect on metabolic activity and DNA synthesis rate of Nalm-6 cells in a dose- and time-dependent manner. Moreover, we found that BIBR1532 exerts an inductive effect on mRNA expression level of Bax, Bad, p73, and p21, which in turn leads to G 1 cell cycle arrest and increased sub-G 1 cell population.
Conclusions
Since treatment with BIBR1532 could arrest the cell cycle activity in Nalm-6 cells and activate cellular apoptotic pathway, anti-telomerase-based therapy may be regarded as a novel promising strategy for ALL treatment.
Key words: Acute Lymphoid Leukemia, BIBR1532, Telomerase
Received: 3 Feb 2016
Accepted: 7 Sep 2016
Correspondence: Bashash D., PhD of Hematology & Blood Banking. Assiatant Professor of Hematology Department, Faculty of Allied Medicine, Shahid Beheshti University of Medical Sciences.
Postal Code: 1971653312, Tehran, Iran. Tel: (+9821) 22721150; Fax: (+9821) 22721150
E-mail:
david_5980@yahoo.com
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Zarei M, Bashash D. Induction of G1 Cell Cycle Arrest and Increased Sub-G1 Population upon Treatment of Nalm-6 Cells with Synthetic Inhibitor of hTERT. Sci J Iran Blood Transfus Organ 2016; 13 (4) :314-323 URL: http://bloodjournal.ir/article-1-1019-en.html
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