title: Quercetin-3-O-(2"-galloyl)-α-l-rhamnopyranoside prevents TRAIL-induced apoptosis in human keratinocytes by suppressing the caspase-8- and Bid-pathways and the mitochondrial pathway.
abstract: Quercetin and its derivatives have antioxidant and anti-inflammatory effects. Nevertheless, in human keratinocytes, compared to the reports on other toxic insults, researches on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis that may be involved in skin diseases are rare. Furthermore, the effect of quercetin-3-O-(2"-galloyl)-α-l-rhamnopyranoside (QGR), a new quercetin derivative, on TRAIL-induced apoptosis in keratinocytes has not been studied. In this respect, we investigated the effect of QGR on TRAIL-induced apoptosis in human keratinocytes. TRAIL triggers apoptosis by inducing a decrease in Bid, Bcl-2, Bcl-xL and survivin protein levels, increase in Bax and VDAC1 levels, loss of the mitochondrial transmembrane potential, release of cytochrome c, activation of caspases (-8, -9 and -3), cleavage of PARP-1, and an increase in the tumor suppressor p53 levels. Treatment with QGR prevented TRAIL-induced apoptosis-related protein activation, formation of reactive oxygen species, nuclear damage, and cell death. In contrast, quercetin induces cytotoxicity and had an additive effect on TRAIL-induced apoptosis-related protein activation and cell death. These results suggest that the QGR, unlike quercetin, may reduce TRAIL-induced apoptosis in human keratinocytes by suppressing the activation of the caspase-8- and Bid-pathways and the mitochondria-mediated cell death pathway, which is associated with the formation of reactive oxygen species. These data suggest that QGR could be effective in the prevention of TRAIL-induced apoptosis-mediated skin diseases.
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, South Korea.
authors.forename: Yun Jeong
authors.initials: YJ
authors.lastname: Kim
authors.forename: Eun Byul
authors.initials: EB
authors.lastname: Jung
authors.forename: Seong Jun
authors.initials: SJ
authors.lastname: Seo
authors.forename: Kwan Hee
authors.initials: KH
authors.lastname: Park
authors.forename: Min Won
authors.initials: MW
authors.lastname: Lee
authors.forename: Chung Soo
authors.initials: CS
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015153:Blotting, Western; D053181:Caspase 8 / Q000378:metabolism*; D061945:Caspase Inhibitors / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology; D008928:Mitochondria / Q000187:drug effects*; D015394:Molecular Structure; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D061945:Caspase Inhibitors; D017382:Reactive Oxygen Species; D053221:TNF-Related Apoptosis-Inducing Ligand; C523166:quercetin 3-O-beta-(2''-galloyl)-rhamnopyranoside; D011794:Quercetin; D053181:Caspase 8
keywords: Apoptosis-related protein activation; Human keratinocytes; QGR; Skin diseases; TRAIL