S-Space College of Medicine/School of Medicine (의과대학/대학원) Molecular and Clinical Oncology (분자종양의학전공) Journal Papers (저널논문_분자종양의학전공)
Alpha-tocopheryl succinate, in contrast to alpha-tocopherol and alpha-tocopheryl acetate, inhibits prostaglandin E2 production in human lung epithelial cells
- Issue Date
- Oxford University Press
- Carcinogenesis. 2006 Nov;27(11):2308-15. Epub 2006 May 19.
- Antioxidants/pharmacology ; Cell Line, Tumor ; Cell Survival ; Dinoprostone/*metabolism ; Disease Progression ; Dose-Response Relationship, Drug ; Epithelial Cells/*metabolism ; Humans ; Inflammation ; Lung/*metabolism ; Reactive Oxygen Species ; Tocopherols ; Vitamin E/*analogs & derivatives/pharmacology ; alpha-Tocopherol/*analogs & derivatives/*pharmacology ; Gene Expression Regulation, Neoplastic
- 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.
- 0143-3334 (Print)
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