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Alpha-tocopheryl succinate, in contrast to alpha-tocopherol and alpha-tocopheryl acetate, inhibits prostaglandin E2 production in human lung epithelial cells

Cited 23 time in Web of Science Cited 25 time in Scopus
Authors
Lee, Eunmyong; Choi, Moon-Kyung; Lee, Young-Ju; Ku, Ja-Lok; Kim, Kyung-Hee; Choi, Jin-Sung; Lim, Soo-Jeong
Issue Date
2006-05-23
Publisher
Oxford University Press
Citation
Carcinogenesis. 2006 Nov;27(11):2308-15. Epub 2006 May 19.
Keywords
Antioxidants/pharmacologyCell Line, TumorCell SurvivalDinoprostone/*metabolismDisease ProgressionDose-Response Relationship, DrugEpithelial Cells/*metabolism*Gene Expression Regulation, NeoplasticHumansInflammationLung/*metabolismReactive Oxygen SpeciesTocopherolsVitamin E/*analogs & derivatives/pharmacologyalpha-Tocopherol/*analogs & derivatives/*pharmacology
Abstract
The production of prostaglandin E2 (PGE2), a key proinflammatory mediator, is regulated by the availability of its substrate, arachidonic acid (AA), and the activity of the enzyme cyclooxygenase (COX). Increased PGE2 production and COX-2 expression have been observed frequently in specimens from lung cancer patients. Agents that decrease PGE2 production may prevent the initiation and progression of lung cancer. We, therefore, tested the effects of alpha-tocopherol (alphaTOL) analogs on PGE2 production in human lung epithelial cells. Alpha-tocopheryl succinate (alphaTOS), but not alphaTOL or alpha-tocopheryl acetate (alphaTOA), inhibited the phorbol 12-myristate 13-acetate (PMA)-stimulated PGE2 production in three human lung epithelial cell lines (BEAS-2B, H460 and A549 cells). The effect of these compounds on PGE2 production was not correlated with their antioxidant activities, since alphaTOS alone did not inhibit PMA-induced generation of reactive oxygen species. alphaTOS had no effect on PMA-induced AA release or COX-2 expression, although post-incubation with alphaTOS inhibited COX activity and prostaglandin (PGE2 and PGF(2alpha)) production in PMA-stimulated cells. alphaTOS also blocked the COX activity in A549 cells with endogenous high levels of COX enzymes in the absence of PMA stimulation. In addition, the ability of alphaTOS to inhibit COX was affected by AA concentration, suggesting that alphaTOS may compete with AA for interaction with COX proteins. These results suggest that alphaTOS inhibits COX activity, thereby inhibiting PGE2 production in human lung epithelial cells, despite the lack of antioxidant activity. Administration of alphaTOS may block inflammatory responses mediated by PGE2, thereby inhibiting the initiation and progression of lung cancer.
ISSN
0143-3334 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16714329

http://hdl.handle.net/10371/47151
DOI
https://doi.org/10.1093/carcin/bgl073
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College of Medicine/School of Medicine (의과대학/대학원)Molecular and Clinical Oncology (분자종양의학전공)Journal Papers (저널논문_분자종양의학전공)
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