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Medical Oncology
Published in: Medical Oncology 3/2010

01-09-2010 | Original Paper

Arsenic trioxide induces apoptosis in NB-4, an acute promyelocytic leukemia cell line, through up-regulation of p73 via suppression of nuclear factor kappa B-mediated inhibition of p73 transcription and prevention of NF-κB-mediated induction of XIAP, cIAP2, BCL-XL and survivin

Authors: Majid Momeny, Majid Zakidizaji, Reza Ghasemi, Ahmad R. Dehpour, Maryam Rahimi_Balaei, Yassan Abdolazimi, Ardeshir Ghavamzadeh, Kamran Alimoghaddam, Seyed H. Ghaffari

Published in: Medical Oncology | Issue 3/2010

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Abstract

The purpose of the present study is to evaluate the effects of arsenic trioxide (ATO) on human acute promyelocytic leukemia NB-4 cells. Microculture tetrazolium test, bromodeoxyuridine (BrdU) cell proliferation assay, caspase 3 activity assay, cell-based nuclear factor kappa B (NF-κB) phosphorylation measurement by ELISA and real-time RT-PCR were employed to appraise the effects of ATO on metabolic activity, DNA synthesis, induction of programmed cell death and NF-κB activation. The suppressive effects of ATO on metabolic potential, cell proliferation and NF-κB activation were associated with induction of apoptosis in NB-4 cells. In addition, an expressive enhancement in mRNA levels of p73, cyclin-dependent kinase inhibitor 1A (p21), tumor protein 53-induced nuclear protein 1 (TP53INP1), WNK lysine deficient protein kinase 2 (WNK2) and lipocalin 2 coupled with a significant reduction in transcriptional levels of NF-κB inhibitor beta (IKK2), Nemo, BCL2-like 1 (BCL-XL), inhibitor of apoptosis protein 1 (cIAP2), X-linked inhibitor of apoptosis protein (XIAP), survivin, Bcl-2, TIP60, ataxia telangiectasia (ATM), SHP-2 and sirtuin (SIRT1) were observed. Altogether, these issues show for the first time that ATO treatment could trammel cell growth and proliferation as well as induces apoptosis in NB-4 cells through induction of transcriptional levels of p73, TP53INP1, WNK2, lipocalin 2 as well as suppression of NF-κB-mediated induction of BCL-XL, cIAP2, XIAP and survivin. Furthermore, the inductionary effects of ATO on transcriptional stimulation of p73 might be through cramping the NF-κB module (through suppression of p65 phosphorylation as well as transcriptional hindering of IKK2, ATM and Nemo) along with diminishing the mRNA expression of TIP60, SHP-2 and SIRT1.
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Metadata
Title
Arsenic trioxide induces apoptosis in NB-4, an acute promyelocytic leukemia cell line, through up-regulation of p73 via suppression of nuclear factor kappa B-mediated inhibition of p73 transcription and prevention of NF-κB-mediated induction of XIAP, cIAP2, BCL-XL and survivin
Authors
Majid Momeny
Majid Zakidizaji
Reza Ghasemi
Ahmad R. Dehpour
Maryam Rahimi_Balaei
Yassan Abdolazimi
Ardeshir Ghavamzadeh
Kamran Alimoghaddam
Seyed H. Ghaffari
Publication date
01-09-2010
Publisher
Springer US
Published in
Medical Oncology / Issue 3/2010
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-009-9294-9

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