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

• Published in: Carcinogenesis (New York) Vol. 27; no. 11; pp. 2308 - 2315
• Main Authors: Lee, Eunmyong, Choi, Moon-Kyung, Lee, Young-Ju, Ku, Ja-Lok, Kim, Kyung-Hee, Choi, Jin-Sung, Lim, Soo-Jeong
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.11.2006; Oxford Publishing Limited (England)
• Subjects: alpha-Tocopherol - analogs & derivatives; alpha-Tocopherol - pharmacology; Antioxidants - pharmacology; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Cell Line, Tumor; Cell Survival; Dinoprostone - metabolism; Disease Progression; Dose-Response Relationship, Drug; Epithelial Cells - metabolism; Gene Expression Regulation, Neoplastic; Humans; Inflammation; Lung - metabolism; Medical sciences; Reactive Oxygen Species; Tocopherols; Tumors; Vitamin E - analogs & derivatives; Vitamin E - pharmacology; Human; Eicosanoid; Arachidonic acid derivatives; Lung; Prostaglandin E2; Epithelial cell; Inhibitor; Acetate; Tocopherol; Respiratory system; In vitro
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgl073

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 (αTOL) analogs on PGE2 production in human lung epithelial cells. Alpha-tocopheryl succinate (αTOS), but not αTOL or alpha-tocopheryl acetate (αTOA), 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 αTOS alone did not inhibit PMA-induced generation of reactive oxygen species. αTOS had no effect on PMA-induced AA release or COX-2 expression, although post-incubation with αTOS inhibited COX activity and prostaglandin (PGE2 and PGF2α) production in PMA-stimulated cells. αTOS 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 αTOS to inhibit COX was affected by AA concentration, suggesting that αTOS may compete with AA for interaction with COX proteins. These results suggest that αTOS inhibits COX activity, thereby inhibiting PGE2 production in human lung epithelial cells, despite the lack of antioxidant activity. Administration of αTOS may block inflammatory responses mediated by PGE2, thereby inhibiting the initiation and progression of lung cancer.