Increased oxidative stress created by adenoviral MnSOD or CuZnSOD plus BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) inhibits breast cancer cell growth

Christine J Weydert; Yuping Zhang; Wenqing Sun; Trent A Waugh; Melissa L.T Teoh; Kelly K Andringa; Nukhet Aykin-Burns; Douglas R Spitz; Brian J Smith; Larry W Oberley

doi:10.1016/j.freeradbiomed.2007.11.009

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Increased oxidative stress created by adenoviral MnSOD or CuZnSOD plus BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) inhibits breast cancer cell growth

Journal article

Peer reviewed

Increased oxidative stress created by adenoviral MnSOD or CuZnSOD plus BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) inhibits breast cancer cell growth

Christine J Weydert, Yuping Zhang, Wenqing Sun, Trent A Waugh, Melissa L.T Teoh, Kelly K Andringa, Nukhet Aykin-Burns, Douglas R Spitz, Brian J Smith and Larry W Oberley

Free radical biology & medicine, Vol.44(5), pp.856-867

2008

DOI: 10.1016/j.freeradbiomed.2007.11.009

PMID: 18155673

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Abstract

Superoxide dismutases (SODs) have been found to decrease tumor formation and angiogenesis. SOD gene therapy, as with many other gene transfer strategies, may not completely inhibit tumor growth on its own. Thus, concomitant therapies are necessary to completely control the spread of this disease. We hypothesized that intratumoral injection of Ad SOD in combination with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) chemotherapy would synergistically inhibit breast cancer growth. Our data indicate that BCNU when combined with SOD overexpression increased oxidative stress as suggested by elevated glutathione disulfide (GSSG) production in one of three breast cancer cell lines tested, at least in part due to glutathione reductase (GR) inactivation. The increased oxidative stress caused by BCNU combined with adenovirally expressed SODs, manganese or copper zinc SOD, decreased growth and survival in the three cell lines tested in vitro, but had the largest effect in the MDA-MB231 cell line, which showed the largest amount of oxidative stress. Delivery of MnSOD and BCNU intratumorally completely inhibited MDA-MB231 xenograft growth and increased nude mouse survival in vivo. Intravenous (iv) BCNU, recapitulating clinical usage, and intratumoral Ad MnSOD delivery, to provide tumor specificity, provided similar decreased growth and survival in our nude mouse model. This cancer therapy produced impressive results, suggesting the potential use of oxidative stress-induced growth inhibitory treatments for breast cancer patients.

Superoxide dismutase

Breast cancer

Adenovirus

Xenografts

BCNU

Details

Title: Subtitle: Increased oxidative stress created by adenoviral MnSOD or CuZnSOD plus BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) inhibits breast cancer cell growth
Creators: Christine J Weydert - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, and Holden Comprehensive Cancer Center (HCCC), The University of Iowa, Iowa City, IA 52242, USA
Yuping Zhang - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, and Holden Comprehensive Cancer Center (HCCC), The University of Iowa, Iowa City, IA 52242, USA
Wenqing Sun - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, and Holden Comprehensive Cancer Center (HCCC), The University of Iowa, Iowa City, IA 52242, USA
Trent A Waugh - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, and Holden Comprehensive Cancer Center (HCCC), The University of Iowa, Iowa City, IA 52242, USA
Melissa L.T Teoh - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, and Holden Comprehensive Cancer Center (HCCC), The University of Iowa, Iowa City, IA 52242, USA
Kelly K Andringa - Department of Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Nukhet Aykin-Burns - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, and Holden Comprehensive Cancer Center (HCCC), The University of Iowa, Iowa City, IA 52242, USA
Douglas R Spitz - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, and Holden Comprehensive Cancer Center (HCCC), The University of Iowa, Iowa City, IA 52242, USA
Brian J Smith - Department of Biostatistics, College of Public Health and Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA 52242, USA
Larry W Oberley - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, and Holden Comprehensive Cancer Center (HCCC), The University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Free radical biology & medicine, Vol.44(5), pp.856-867
DOI: 10.1016/j.freeradbiomed.2007.11.009
PMID: 18155673
NLM abbreviation: Free Radic Biol Med
ISSN: 0891-5849
eISSN: 1873-4596
Publisher: Elsevier Inc
Language: English
Date published: 2008
Academic Unit: Pathology; Biostatistics; Orthopedics and Rehabilitation; Radiation Oncology; Obstetrics and Gynecology; Holden Comprehensive Cancer Center
Record Identifier: 9983997357602771

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