| Overexpression of COX-2 in human osteosarcoma cells decreases proliferation and increases apoptosis. | |
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MedLine Citation:
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PMID: 16818639 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Overexpression of cyclooxygenase-2 (COX-2) is generally considered to promote tumorigenesis. To investigate a potential role of COX-2 in osteosarcoma, we overexpressed COX-2 in human osteosarcoma cells. Saos-2 cells deficient in COX-2 expression were retrovirally transduced or stably transfected with murine COX-2 cDNA. Functional expression of COX-2 was confirmed by Northern and Western analyses and prostaglandin production. Overexpression of COX-2 reduced cell numbers by 50% to 70% compared with controls. Decreased proliferation in COX-2-overexpressing cells was associated with cell cycle prolongation in G(2)-M. Apoptosis, measured by both Annexin V binding assay and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling staining, was increased in cells overexpressing COX-2, and the increase was not reversed by treatment with NS-398, indicating that the effects were not mediated by prostaglandins. Retroviral COX-2 overexpression in two other human osteosarcoma cell lines, U2OS and TE85, also decreased cell viability. However, in the human colon carcinoma HCT-116 cell line, which is deficient in COX-2, retroviral overexpression of COX-2, at similar efficiency as in Saos-2 cells, increased resistance to apoptosis. Reactive oxygen species (ROS), measured by flow cytometry, were increased by COX-2 overexpression in Saos-2 cells but not in HCT-116 cells. Inhibition of peroxidase activity, but not of COX activity, blocked the ROS increase. Antioxidants blocked the increase in ROS and the increase in apoptosis due to COX-2 overexpression in Saos-2 cells. Our results suggest that (a) COX-2 overexpression in osteosarcoma cells may increase resistance to tumorigenesis by increasing ROS to levels that decrease cell viability and (b) the effects of COX-2 overexpression are cell type/tissue dependent. |
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Authors:
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Zheng Xu; Shilpa Choudhary; Olga Voznesensky; Meenal Mehrotra; Monica Woodard; Marc Hansen; Harvey Herschman; Carol Pilbeam |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cancer research Volume: 66 ISSN: 0008-5472 ISO Abbreviation: Cancer Res. Publication Date: 2006 Jul |
Date Detail:
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Created Date: 2006-07-04 Completed Date: 2006-09-07 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 6657-64 Citation Subset: IM |
Affiliation:
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Department of Medicine, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antioxidants
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pharmacology Apoptosis / physiology Bone Neoplasms / enzymology*, genetics, pathology* Cell Growth Processes / physiology Cell Line, Tumor Cyclooxygenase 2 / biosynthesis*, genetics Dinoprostone / pharmacology HCT116 Cells Humans Osteosarcoma / enzymology*, genetics, pathology* Reactive Oxygen Species / metabolism Retroviridae / genetics Transduction, Genetic Transfection |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK 48361/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Reactive Oxygen Species; 363-24-6/Dinoprostone; EC 1.14.99.1/Cyclooxygenase 2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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