Cyclooxygenase-2/prostaglandin E₂ inducing effects of α-tocopheryl polyethylene glycol succinate in lung epithelial cells.
Tocopherol analogs are known to have pleiotropic effects due to its interaction with diverse intracellular targets. Previously we reported that low/subapoptotic dose of α-tocopheryl succinate (αTOS) inhibits cyclooxygenase (COX) and prostaglandin E₂ (PGE₂) production in lung epithelial cells, while high dose of αTOS induces the reactive oxygen species (ROS) generation and apoptosis. In our separate study, we demonstrated that α-tocopheryl polyethylene glycol succinate (αTPGS), a polyethylene glycol (PEG)-conjugated derivative of αTOS, is a more potent ROS/apoptosis inducer compared with αTOS. The present study was prompted to examine whether PEG conjugation to αTOS also enforced its COX inhibitory activity. Of interest, we found that αTPGS failed to inhibit COX activity regardless of doses, suggesting that PEG conjugation to αTOS resulted in the loss of its COX inhibitory activity. Unexpectedly, αTPGS rather induced the COX-2 protein expression at higher/apoptotic doses. αTPGS-induced COX-2 expression was inhibited by antioxidant pretreatment. These data indicate that the COX-2 induction by αTPGS is mediated through increased ROS generation. Since the use of αTPGS as a surfactant component of dispersive drug delivery systems is frequently considered, caution should be taken when the drugs involved in COX signaling are loaded in αTPGS-included delivery systems.
Department of Bioscience and Biotechnology, Sejong University, Seoul, 143-747, Korea.
Eun-Hye
EH
Lee
Soo-Jeong
SJ
Lim
D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000378:metabolism; D019587:Dietary Supplements; D015232:Dinoprostone / Q000378:metabolism*; D004790:Enzyme Induction; D005079:Excipients / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000201:enzymology / Q000378:metabolism*; D009994:Osmolar Concentration; D018384:Oxidative Stress; D011092:Polyethylene Glycols / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D020545:Respiratory Mucosa / Q000201:enzymology / Q000378:metabolism*; D013501:Surface-Active Agents / Q000378:metabolism; D015854:Up-Regulation; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000378:metabolism; D024502:alpha-Tocopherol / Q000378:metabolism
D000975:Antioxidants; D052246:Cyclooxygenase 2 Inhibitors; D005079:Excipients; D017382:Reactive Oxygen Species; D013501:Surface-Active Agents; D014810:Vitamin E; D011092:Polyethylene Glycols; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D024502:alpha-Tocopherol; D015232:Dinoprostone; C014225:tocophersolan