Inhibition of oral cancer cell growth by adenovirusMnSOD plus BCNU treatment

Christine J Darby Weydert; Benjamin B Smith; Linjing Xu; Kevin C Kregel; Justine M Ritchie; Charles S Davis; Larry W Oberley

doi:10.1016/S0891-5849(02)01245-5

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Inhibition of oral cancer cell growth by adenovirusMnSOD plus BCNU treatment

Journal article

Peer reviewed

Inhibition of oral cancer cell growth by adenovirusMnSOD plus BCNU treatment

Christine J Darby Weydert, Benjamin B Smith, Linjing Xu, Kevin C Kregel, Justine M Ritchie, Charles S Davis and Larry W Oberley

Free radical biology & medicine, Vol.34(3), pp.316-329

02/01/2003

DOI: 10.1016/S0891-5849(02)01245-5

PMID: 12543247

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Abstract

We hypothesized that inhibitors of peroxide removal, such as BCNU, an indirect inhibitor of glutathione peroxidase (GPx), and 3-amino-1,2,4-triazole (AT), a direct inhibitor of catalase (CAT), should cause toxicity to cancer cells after manganese superoxide dismutase (MnSOD) overexpression due to elevated peroxide levels. In vitro, hamster cheek pouch carcinoma cells (HCPC-1) and human oral squamous carcinoma cells (SCC-25) were infected with various combinations of adenovirus containing MnSOD cDNA (AdMnSOD). Cells were then treated with or without BCNU and assayed for viability using Annexin/PI staining and flow cytometry. In AdMnSOD plus BCNU-treated SCC-25 and HCPC-1 cells, a 30-60% decrease in cell viability was observed compared to BCNU alone. In vivo, HCPC-1 and SCC-25 xenografts were allowed to grow to approximately 70 mm(3) and 10(9) plaque forming units (pfu) of AdMnSOD were injected directly into the tumors. Two days later, 15 or 30 mg/kg BCNU was injected intratumorally. Tumor growth was greatly inhibited (4- to 20-fold) by this combined treatment, as well as increasing animal survival. Tumor volume could be decreased further by giving multiple doses of AdMnSOD or inhibiting catalase activity with AT. These results suggest that, by using these combination therapies, a significant decrease in tumor mass can be achieved.

Adenoviridae - genetics

Animals

Antioxidants - metabolism

Carmustine - pharmacology

Catalase - antagonists & inhibitors

Cattle

Cell Division - drug effects

Cell Transformation, Neoplastic

Combined Modality Therapy

Cricetinae

Genetic Therapy

Humans

Mouth Neoplasms - drug therapy

Mouth Neoplasms - pathology

Superoxide Dismutase - genetics

Superoxide Dismutase - metabolism

Tumor Cells, Cultured

Details

Title: Subtitle: Inhibition of oral cancer cell growth by adenovirusMnSOD plus BCNU treatment
Creators: Christine J Darby 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, The University of Iowa, Iowa City, IA 52242, USA
Benjamin B Smith
Linjing Xu
Kevin C Kregel
Justine M Ritchie
Charles S Davis
Larry W Oberley
Resource Type: Journal article
Publication Details: Free radical biology & medicine, Vol.34(3), pp.316-329
DOI: 10.1016/S0891-5849(02)01245-5
PMID: 12543247
NLM abbreviation: Free Radic Biol Med
ISSN: 0891-5849
eISSN: 1873-4596
Grant note: P01 CA66081 / NCI NIH HHS P50 DE10758 / NIDCR NIH HHS
Language: English
Date published: 02/01/2003
Academic Unit: Radiation Oncology; Provost Office Administration; Otolaryngology; Health, Sport, and Human Physiology
Record Identifier: 9984213308802771

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