Document Detail

Bcl-2 switches the type of demise from apoptosis to necrosis via cyclooxygenase-2 upregulation in HeLa cell induced by hydrogen peroxide.
MedLine Citation:
PMID:  16458114     Owner:  NLM     Status:  MEDLINE    
Bcl-2 is best known for its anti-apoptotic function in a wide variety of cell types. The objective of this study was to investigate the effects of bcl-2 on the types of cell demise in the HeLa/bcl-2 cells induced by H2O2. The HeLa cell expressed stably bcl-2 was established and defined as the HeLa/bcl-2 cell strain, while the cell transfected with the empty expression vector was defined as the HeLa/vector cell strain. MTT assay revealed that the HeLa/bcl-2 cells showed a shorter life span. BrdU incorporation assay indicated that the bcl-2 exerted anti-demise effect on the HeLa/bcl-2 cells at the low concentration of H2O2. However, at the high concentration of H2O2, the death of the HeLa/bcl-2 cells was more than that of the HeLa/vector cells. The flow cytometry demonstrated that H2O2 mainly induced apoptosis in the HeLa/vector cells and elicited necrosis in the HeLa/bcl-2 cells. The addition of celecoxib to the cells treated by H2O2 could increase apoptosis in the HeLa/vector cells and convert necrosis into apoptosis in the HeLa/bcl-2 cells. The higher levels of cellular free radical and GSH were found in the HeLa/bcl-2 cells, but not in the HeLa/vector cells. With 200 microM H2O2 challenge for 48 h, the level of the cellular free radical was increased in the both strains, while the level of the GSH was decreased in the both strains. Celecoxib could reverse the difference between the both strains led by H2O2. Western blotting showed that the expression of COX-2 was always higher in the HeLa/bcl-2 cells than in the HeLa/vector cells under the both of treated and untreated with H2O2, while the level of COX-1 was relative stable in the both strains. These results suggested that the crosstalk between the bcl-2 and the COX-2 pathways could exist, the bcl-2 might up-regulate COX-2 to modify sensitivity to the types of demise in the HeLa/bcl-2 cell.
Gang-Jun Du; Hai-Hong Lin; Qi-Tai Xu; Min-Wei Wang
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cancer letters     Volume:  232     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-02-06     Completed Date:  2006-04-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  179-88     Citation Subset:  IM    
Department of Pharmacology, Pharmacy College of He-nan University, West gate street 357, Kaifeng 475001, He-nan, China.
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MeSH Terms
Apoptosis / drug effects*
Cyclooxygenase 2 / analysis,  biosynthesis*
Cytochromes c / secretion
Glutathione / analysis
Hela Cells
Hydrogen Peroxide / pharmacology*
Proto-Oncogene Proteins c-bcl-2 / analysis,  physiology*
Reg. No./Substance:
0/Proto-Oncogene Proteins c-bcl-2; 70-18-8/Glutathione; 7722-84-1/Hydrogen Peroxide; 9007-43-6/Cytochromes c; EC 2

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