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Tumor Biology
Published in: Tumor Biology 11/2015

01-11-2015 | Research Article

MST-312 induces G2/M cell cycle arrest and apoptosis in APL cells through inhibition of telomerase activity and suppression of NF-κB pathway

Authors: Ahmad Fatemi, Majid Safa, Ahmad Kazemi

Published in: Tumor Biology | Issue 11/2015

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Abstract

Telomerase-targeted therapy for cancer has received great attention because telomerase is expressed in almost all cancer cells but is inactive in most normal somatic cells. This study was aimed to investigate the effects of telomerase inhibitor MST-312, a chemically modified derivative of epigallocatechin gallate (EGCG), on acute promyelocytic leukemia (APL) cells. Our results showed that MST-312 exerted a dose-dependent short-term cytotoxic effect on APL cells, with G2/M cell cycle arrest. Moreover, MST-312 induced apoptosis of APL cells in caspase-mediated manner. Telomeric repeat amplification protocol (TRAP) assay revealed significant reduction in telomerase activity of APL cells following short-term exposure to MST-312. Interestingly, MST-312-induced telomerase inhibition was coupled with suppression of NF-κB activity as evidenced by inhibition of IκBα phosphorylation and its degradation and decreased NF-κB DNA binding activity. In addition, gene expression analysis showed downregulation of genes regulated by NF-κB, such as antiapoptotic (survivin, Bcl-2, Mcl-1), proliferative (c-Myc), and telomerase-related (hTERT) genes. Importantly, MST-312 did not show any apoptotic effect in normal human peripheral blood mononuclear cells (PBMCs). In conclusion, our data suggest that dual inhibition of telomerase activity and NF-κB pathway by MST-312 represents a novel treatment strategy for APL.
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Metadata
Title
MST-312 induces G2/M cell cycle arrest and apoptosis in APL cells through inhibition of telomerase activity and suppression of NF-κB pathway
Authors
Ahmad Fatemi
Majid Safa
Ahmad Kazemi
Publication date
01-11-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 11/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3575-z

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