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-kappaB-mediated induction of XIAP, cIAP2, BCL-XL and survivin.
| 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-kappaB) 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-kappaB activation. The suppressive effects of ATO on metabolic potential, cell proliferation and NF-kappaB 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-kappaB inhibitor beta (IKK2), Nemo, BCL2-like 1 (BCL-X(L)), 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-kappaB-mediated induction of BCL-X(L), cIAP2, XIAP and survivin. Furthermore, the inductionary effects of ATO on transcriptional stimulation of p73 might be through cramping the NF-kappaB 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. |
| Authors | Majid Momeny, Majid Zakidizaji, Reza Ghasemi, Ahmad R Dehpour, Maryam Rahimi-Balaei, Yassan Abdolazimi, Ardeshir Ghavamzadeh, Kamran Alimoghaddam, Seyed H Ghaffari |
| Journal | Medical oncology (Northwood, London, England)
(Med Oncol)
Vol. 27
Issue 3
Pg. 833-42
(Sep 2010)
ISSN: 1559-131X [Electronic] United States |
| PMID | 19763917
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Acute-Phase Proteins
- Arsenicals
- BCL2L1 protein, human
- BIRC5 protein, human
- CDKN1A protein, human
- Carrier Proteins
- Cell Cycle Proteins
- Cyclin-Dependent Kinase Inhibitor p21
- DNA-Binding Proteins
- Heat-Shock Proteins
- IKBKG protein, human
- Inhibitor of Apoptosis Proteins
- LCN2 protein, human
- Lipocalin-2
- Lipocalins
- Microtubule-Associated Proteins
- NF-kappa B
- Neoplasm Proteins
- Nuclear Proteins
- Oxides
- Proto-Oncogene Proteins
- RNA, Messenger
- RNA, Neoplasm
- Survivin
- TP53INP1 protein, human
- TP73 protein, human
- Tumor Protein p73
- Tumor Suppressor Proteins
- X-Linked Inhibitor of Apoptosis Protein
- XIAP protein, human
- bcl-X Protein
- Histone Acetyltransferases
- KAT5 protein, human
- Lysine Acetyltransferase 5
- BIRC3 protein, human
- Baculoviral IAP Repeat-Containing 3 Protein
- Ubiquitin-Protein Ligases
- WNK2 protein, human
- ATM protein, human
- Ataxia Telangiectasia Mutated Proteins
- Protein Serine-Threonine Kinases
- I-kappa B Kinase
- PTPN11 protein, human
- Protein Tyrosine Phosphatase, Non-Receptor Type 11
- Caspase 3
- SIRT1 protein, human
- Sirtuin 1
- Arsenic Trioxide
|
| Topics |
- Acute-Phase Proteins
(biosynthesis, genetics)
- Apoptosis
(drug effects)
- Arsenic Trioxide
- Arsenicals
(pharmacology)
- Ataxia Telangiectasia Mutated Proteins
- Baculoviral IAP Repeat-Containing 3 Protein
- Carrier Proteins
(biosynthesis, genetics)
- Caspase 3
(biosynthesis, genetics)
- Cell Cycle Proteins
(biosynthesis, genetics)
- Cell Line, Tumor
(drug effects, metabolism, pathology)
- Cyclin-Dependent Kinase Inhibitor p21
(biosynthesis, genetics)
- DNA-Binding Proteins
(biosynthesis, genetics)
- Gene Expression Regulation, Neoplastic
(drug effects)
- Heat-Shock Proteins
(biosynthesis, genetics)
- Histone Acetyltransferases
(biosynthesis, genetics)
- Humans
- I-kappa B Kinase
(biosynthesis, genetics)
- Inhibitor of Apoptosis Proteins
(biosynthesis, genetics)
- Lipocalin-2
- Lipocalins
(biosynthesis, genetics)
- Lysine Acetyltransferase 5
- Microtubule-Associated Proteins
(biosynthesis, genetics)
- NF-kappa B
(antagonists & inhibitors)
- Neoplasm Proteins
(biosynthesis, genetics)
- Nuclear Proteins
(biosynthesis, genetics)
- Oxides
(pharmacology)
- Protein Serine-Threonine Kinases
(biosynthesis, genetics)
- Protein Tyrosine Phosphatase, Non-Receptor Type 11
(biosynthesis, genetics)
- Proto-Oncogene Proteins
(biosynthesis, genetics)
- RNA, Messenger
(biosynthesis, genetics)
- RNA, Neoplasm
(biosynthesis, genetics)
- Sirtuin 1
(biosynthesis, genetics)
- Survivin
- Transcription, Genetic
(drug effects)
- Tumor Protein p73
- Tumor Suppressor Proteins
(biosynthesis, genetics)
- Ubiquitin-Protein Ligases
- X-Linked Inhibitor of Apoptosis Protein
(biosynthesis, genetics)
- bcl-X Protein
(biosynthesis, genetics)
|
|
Join CureHunter, for free Research Interface BASIC access!
Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease.
Find out why thousands of doctors, pharma researchers and patient activists
around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!
|
