Modulation of reactive oxygen species in pancreatic cancer

Melissa L T Teoh; Wenqing Sun; Brian J Smith; Larry W Oberley; Joseph J Cullen

doi:10.1158/1078-0432.CCR-07-0851

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Modulation of reactive oxygen species in pancreatic cancer

Journal article

Open access

Peer reviewed

Modulation of reactive oxygen species in pancreatic cancer

Melissa L T Teoh, Wenqing Sun, Brian J Smith, Larry W Oberley and Joseph J Cullen

Clinical cancer research, Vol.13(24), pp.7441-7450

12/15/2007

DOI: 10.1158/1078-0432.CCR-07-0851

PMID: 18094428

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https://doi.org/10.1158/1078-0432.CCR-07-0851View

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Abstract

The aim of the present study was to compare the effects of the three different forms of the antioxidant enzyme superoxide dismutase [i.e., manganese superoxide dismutase (MnSOD), copper zinc superoxide dismutase (CuZnSOD), and extracellular superoxide dismutase (EcSOD)] on the malignant phenotype of human pancreatic cancer. Human pancreatic cancer cell lines were infected with adenoviral vectors containing the cDNAs for three different forms of the antioxidant enzyme SOD. Intratumoral injections of the adenoviral vectors were used in nude mice with human tumor xenografts. Increases in immunoreactive protein and enzymatic activity were seen after infections with the AdMnSOD, AdCuZnSOD, or AdEcSOD constructs. Increased SOD activity decreased superoxide levels and increased hydrogen peroxide levels. Increasing SOD levels correlated with increased doubling time. Cell growth and plating efficiency decreased with increasing amounts of the adenoviral constructs, with the AdCuZnSOD vector having the greatest effect in decreasing in vitro tumor growth. In contrast, inhibiting endogenous SOD with small interfering RNA increased superoxide levels and promoted tumor growth. Of the three SODs, tumors grew the slowest and survival was increased the greatest in nude mice injected with the AdEcSOD construct. Scavenging plasma membrane-generated superoxide may prove beneficial for suppression of pancreatic cancer growth.

Superoxide Dismutase - genetics

Reactive Oxygen Species - metabolism

Humans

Pancreatic Neoplasms - pathology

Pancreatic Neoplasms - enzymology

Blotting, Western

Xenograft Model Antitumor Assays

Animals

Flow Cytometry

Transfection

Isoenzymes - metabolism

Mice, Nude

Cell Line, Tumor

Mice

RNA, Small Interfering

Superoxide Dismutase - metabolism

Details

Title: Subtitle: Modulation of reactive oxygen species in pancreatic cancer
Creators: Melissa L T Teoh - Department of Surgery and Radiation Oncology, University of Iowa College of Medicine, Iowa City, IA 52242, USA
Wenqing Sun
Brian J Smith
Larry W Oberley
Joseph J Cullen
Resource Type: Journal article
Publication Details: Clinical cancer research, Vol.13(24), pp.7441-7450
DOI: 10.1158/1078-0432.CCR-07-0851
PMID: 18094428
NLM abbreviation: Clin Cancer Res
ISSN: 1078-0432
eISSN: 1557-3265
Publisher: United States
Grant note: CA115785 / NCI NIH HHS CA66081 / NCI NIH HHS
Language: English
Date published: 12/15/2007
Academic Unit: Biostatistics; Surgery; Radiation Oncology; Holden Comprehensive Cancer Center
Record Identifier: 9983997478902771

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