Document Detail

Overexpression of COX-2 in human osteosarcoma cells decreases proliferation and increases apoptosis.
MedLine Citation:
PMID:  16818639     Owner:  NLM     Status:  MEDLINE    
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.
Zheng Xu; Shilpa Choudhary; Olga Voznesensky; Meenal Mehrotra; Monica Woodard; Marc Hansen; Harvey Herschman; Carol Pilbeam
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  66     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-07-04     Completed Date:  2006-09-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6657-64     Citation Subset:  IM    
Department of Medicine, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA.
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MeSH Terms
Antioxidants / pharmacology
Apoptosis / physiology
Bone Neoplasms / enzymology*,  genetics,  pathology*
Cell Growth Processes / physiology
Cell Line, Tumor
Cyclooxygenase 2 / biosynthesis*,  genetics
Dinoprostone / pharmacology
HCT116 Cells
Osteosarcoma / enzymology*,  genetics,  pathology*
Reactive Oxygen Species / metabolism
Retroviridae / genetics
Transduction, Genetic
Grant Support
Reg. No./Substance:
0/Antioxidants; 0/Reactive Oxygen Species; 363-24-6/Dinoprostone; EC 2

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