Journal article
Extracellular Superoxide and the Growth of Pancreatic Carcinoma
Current cancer therapy reviews, Vol.9(4), pp.278-283
01/01/2013
DOI: 10.2174/157339470904140418095056
Abstract
Adenocarcinoma of the pancreas is the fourth leading cause of cancer-related death in the United States. Therapeutic responsiveness of pancreatic cancer to surgery, chemotherapy, and radiation therapy is poor, resulting in a dismal 5-year survival of less than 3%. Point mutation of the K-ras oncogene is a common event in the early development of pancreatic cancer. Indeed, K-ras mutations occur in up to 95% of pancreatic cancers, with a resulting overall increase in production of reactive oxygen species (ROS) through the activation of NADPH oxidase (NOX). Specifically, the extracellular (non-mitochondrial) generation of superoxide (O-2(center dot-)) from the NOX system results in cell growth and tumor progression. Extracellular superoxide dismutase (SOD3, EcSOD) is the only isoform of superoxide dismutase (SOD) expressed extracellularly. It modulates ROS by converting O-2(center dot-) into hydrogen peroxide (H2O2). Antioxidant enzymes that scavenge specific ROS have inhibited the in vitro and in vivo growth of pancreatic cancer. It has been demonstrated that overexpression of EcSOD inhibits pancreatic cancer cell growth and intracellular signaling pathways. Therefore, we propose that strategies to scavenge non-mitochondrial-generated superoxide may prove beneficial in the treatment pancreatic cancer. This review will focus on the role of O-2(center dot-) as a pro-tumorigenic signaling molecule, including its generation and hypothesized mechanism of action, as well as the role of EcSOD in inhibiting tumor growth and propagation, and its potential as a targeted pancreatic cancer therapy.
Details
- Title: Subtitle
- Extracellular Superoxide and the Growth of Pancreatic Carcinoma
- Creators
- John A. Cieslak - Univ Iowa, Coll Med, Dept Radiat Oncol, Iowa City, IA USAJoseph J. Cullen - Univ Iowa, Coll Med, Dept Surg, Iowa City, IA 52242 USA
- Resource Type
- Journal article
- Publication Details
- Current cancer therapy reviews, Vol.9(4), pp.278-283
- Publisher
- Bentham Science Publ Ltd
- DOI
- 10.2174/157339470904140418095056
- ISSN
- 1573-3947
- eISSN
- 1875-6301
- Number of pages
- 6
- Grant note
- CA166800; CA078586 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Susan L. Bader Foundation of Hope 1I01BX001318-01A2 / Medical Research Service, Department of Veterans Affairs; US Department of Veterans Affairs
- Language
- English
- Date published
- 01/01/2013
- Academic Unit
- Surgery; Radiation Oncology
- Record Identifier
- 9984312982502771
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