title: 3,4,5-Tricaffeoylquinic Acid Attenuates TRAIL-induced Apoptosis in Human Keratinocytes by Suppressing Apoptosis-related Protein Activation.
abstract: Caffeoyl derivatives exhibit antiinflammatory and antioxidant effects. However, the effect of 3,4,5-tricaffeoylquinic acid on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in keratinocytes that may be involved in skin diseases has not been studied. In this respect, we investigated the effect of 3,4,5-tricaffeoylquinic acid on TRAIL-induced apoptosis in human keratinocytes. 3,4,5-Tricaffeoylquinic acid and oxidant scavengers attenuated the decrease in the cytosolic levels of Bid, Bcl-2, and survivin proteins; the increase in the levels of cytosolic Bax, p53, and phosphorylated p53; the increase in the levels of phosphorylated p38; the increase in the mitochondrial levels of the voltage-dependent anion channel; loss of the mitochondrial transmembrane potential; the release of cytochrome c; activation of caspases (8, 9, and 3); cleavage of poly [ADP-ribose] polymerase-1; production of reactive oxygen species; the depletion of glutathione (GSH); nuclear damage; and cell death in keratinocytes treated with TRAIL. These results suggest that 3,4,5-tricaffeoylquinic acid 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. The effect appears to be associated with the inhibitory effect on the production of reactive oxygen species and depletion of GSH. 3,4,5-Tricaffeoylquinic acid appears to be effective in the prevention of TRAIL-induced apoptosis-mediated skin diseases.
authors.affiliation: Department of Pharmacology, College of Medicine, and the BK21plus Skin Barrier Network Human Resources Development Team, Chung-Ang University, Seoul, 156-756, South Korea.
authors.forename: Da Hee
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine, and the BK21plus Skin Barrier Network Human Resources Development Team, Chung-Ang University, Seoul, 156-756, South Korea.
authors.forename: Yoon Jeong
authors.initials: YJ
authors.lastname: Nam
authors.affiliation: Department of Internal Medicine, Soon Chun Hyang University Hospital, Bucheon City, Kyung-Gi-Do, 420-767, South Korea.
authors.forename: Min Sung
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Chung-Ang University Hospital, Seoul, 156-755, South Korea.
authors.forename: Dong Suep
authors.initials: DS
authors.lastname: Sohn
authors.affiliation: Department of Pharmacology, College of Medicine, and the BK21plus Skin Barrier Network Human Resources Development Team, Chung-Ang University, Seoul, 156-756, South Korea.
authors.forename: Yong Kyoo
authors.initials: YK
authors.lastname: Shin
authors.affiliation: Department of Pharmacology, College of Medicine, and the BK21plus Skin Barrier Network Human Resources Development Team, Chung-Ang University, Seoul, 156-756, South Korea.
authors.forename: Chung Soo
authors.initials: CS
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*
chemical_list: D017382:Reactive Oxygen Species; D053221:TNF-Related Apoptosis-Inducing Ligand; C472707:caffeoylquinic acid; D011801:Quinic Acid; D045304:Cytochromes c; D053181:Caspase 8; D020169:Caspases; D005978:Glutathione
keywords: 3,4,5-tricaffeoylquinic acid; TRAIL; apoptosis-related protein activation; human keratinocytes; skin diseases