Document Detail

Manganese superoxide dismutase overexpression changes plating efficiency bidirectionally according to change in redox for SaOS2 human osteosarcoma cell line.
MedLine Citation:
PMID:  15753978     Owner:  NLM     Status:  MEDLINE    
Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme that converts cytotoxic superoxide radicals into hydrogen peroxide. MnSOD activity is lower in tumor cells, and MnSOD overexpression reportedly ameliorates malignant phenotypes. We established stable MnSOD overexpressing cell lines from a human osteosarcoma cell line, SaOS2, and then investigated the effects of MnSOD overexpression on plating efficiency (PE) and the involvement of reactive oxygen species, including nitric oxide (NO) in those effects. The PE of SaOS2FM(L), a moderate MnSOD overexpression cell line, increased, while that of SaOS2FM(H), a high MnSOD overexpression cell line, decreased. Although we assessed PE using a colony-formation assay, time-lapse microscopic observation revealed that cells attached to the flasks had undergone neither apoptosis nor necrosis. Moreover, MnSOD overexpression did not affect cell doubling time. Therefore, MnSOD overexpression might correlate directly with cellular adhesion's effect on PE changes. When L-buthionine-[S,R]-sulfoximine (BSO) was administered to increase the intracellular concentration of hydrogen peroxide, the PEs of both cell lines decreased, and when hydrogen peroxide was eliminated by the administration of sodium pyruvate, only the PE of SaOS2FM(H) increased. The combination of BSO and NO (NOR4 or isosorbide 5-mononitrate) administration synergistically decreased PE in both cell lines. These findings suggest that changes in cellular adhesion properties correlate with the balance between increased hydrogen peroxide levels and decreased superoxide radical levels. This is the first report to indicate that PE and cellular adhesion properties change bidirectionally according to the levels of MnSOD overexpression: first increasing then decreasing as MnSOD activity increases. Our results indicate that PE changes might be decided by the balance between two cytotoxic compounds (decreased superoxide radical levels and increased hydrogen peroxide levels), and that NO loading and increased hydrogen peroxide synergistically reduce PE and cellular adhesion.
Megumi Komatsu; Masahiro Kuroda; Yadi Wang; Daret St Clair; Muneyasu Urano; Shiro Akaki; Jun-Ichi Asaumi; Shoji Kawasaki; Yoshio Hiraki; Susumu Kanazawa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of oncology     Volume:  26     ISSN:  1019-6439     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-03-08     Completed Date:  2005-07-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  853-62     Citation Subset:  IM    
Department of Radiology, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
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MeSH Terms
Bone Neoplasms / enzymology*,  pathology
Cell Adhesion / drug effects*
Colony-Forming Units Assay
Gene Expression Regulation, Neoplastic*
Genes, p53
Hydrogen Peroxide / pharmacology
Nitric Oxide / pharmacology
Osteosarcoma / enzymology*,  pathology*
Oxidants / chemistry
Reactive Oxygen Species / pharmacology
Superoxide Dismutase / biosynthesis*,  pharmacology*
Tumor Cells, Cultured
Reg. No./Substance:
0/Oxidants; 0/Reactive Oxygen Species; 10102-43-9/Nitric Oxide; 7722-84-1/Hydrogen Peroxide; EC Dismutase

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