Redox balance influences differentiation status of neuroblastoma in the presence of all-trans retinoic acid

Anne M Silvis; Michael L McCormick; Douglas R Spitz; Kinsley K Kiningham

doi:10.1016/j.redox.2015.11.012

Back

Redox balance influences differentiation status of neuroblastoma in the presence of all-trans retinoic acid

Journal article

Open access

Peer reviewed

Redox balance influences differentiation status of neuroblastoma in the presence of all-trans retinoic acid

Anne M Silvis, Michael L McCormick, Douglas R Spitz and Kinsley K Kiningham

Redox biology, Vol.7(C), pp.88-96

04/2016

DOI: 10.1016/j.redox.2015.11.012

PMCID: PMC4683430

PMID: 26678800

Files and links (1)

url

https://doi.org/10.1016/j.redox.2015.11.012View

Published (Version of record) Open Access

Abstract

Neuroblastoma is the most common extra-cranial solid tumor in childhood; and patients in stage IV of the disease have a high propensity for tumor recurrence. Retinoid therapy has been utilized as a means to induce differentiation of tumor cells and to inhibit relapse. In this study, the expression of a common neuronal differentiation marker [neurofilament M (NF-M)] in human SK-N-SH neuroblastoma cells treated with 10μM all-trans retinoic acid (ATRA) showed significantly increased expression in accordance with reduced cell number. This was accompanied by an increase in MitoSOX and DCFH2 oxidation that could be indicative of increased steady-state levels of reactive oxygen species (ROS) such as O2(•-) and H2O2, which correlated with increased levels of MnSOD activity and immuno-reactive protein. Furthermore PEG-catalase inhibited the DCFH2 oxidation signal to a greater extent in the ATRA-treated cells (relative to controls) at 96h indicating that as the cells became more differentiated, steady-state levels of H2O2 increased in the absence of increases in peroxide-scavenging antioxidants (i.e., glutathione, glutathione peroxidase, and catalase). In addition, ATRA-induced stimulation of NF-M at 48 and 72h was enhanced by decreasing SOD activity using siRNA directed at MnSOD. Finally, treatment with ATRA for 96h in the presence of MnSOD siRNA or PEG-catalase inhibited ATRA induced increases in NF-M expression. These results provide strong support for the hypothesis that changes in steady-state levels of O2(•-) and H2O2 significantly contribute to the process of ATRA-induced differentiation in neuroblastoma, and suggest that retinoid therapy for neuroblastoma could potentially be enhanced by redox-based manipulations of superoxide metabolism to improve patient outcome.

Fluoresceins - chemistry

Oxidation-Reduction

Humans

Hydrogen Peroxide - pharmacology

Cell Differentiation - drug effects

Neuroblastoma - drug therapy

SOX Transcription Factors - metabolism

Cell Line, Tumor

Antineoplastic Agents - pharmacology

Neuroblastoma - metabolism

Gene Expression Regulation, Neoplastic - drug effects

Neurofilament Proteins - metabolism

Tretinoin - pharmacology

Details

Title: Subtitle: Redox balance influences differentiation status of neuroblastoma in the presence of all-trans retinoic acid
Creators: Anne M Silvis - Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA
Michael L McCormick - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City 52242, USA
Douglas R Spitz - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City 52242, USA
Kinsley K Kiningham - Department of Pharmaceutical, Social, and Administrative Sciences, Belmont University College of Pharmacy, 1900 Belmont Boulevard, Nashville, TN 37212, USA. Electronic address: kelley.kiningham@belmont.edu
Resource Type: Journal article
Publication Details: Redox biology, Vol.7(C), pp.88-96
DOI: 10.1016/j.redox.2015.11.012
PMID: 26678800
PMCID: PMC4683430
NLM abbreviation: Redox Biol
ISSN: 2213-2317
eISSN: 2213-2317
Publisher: Netherlands
Grant note: P30 ES005605 / NIEHS NIH HHS 1P20RR020180 / NCRR NIH HHS P20 RR020180 / NCRR NIH HHS P30CA086862 / NCI NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 04/2016
Academic Unit: Pathology; Radiation Oncology
Record Identifier: 9984047785002771

Metrics

10 Record Views

24 Times Cited - Web of Science