Polyphenol acertannin prevents TRAIL-induced apoptosis in human keratinocytes by suppressing apoptosis-related protein activation.
The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has been implicated in the inflammatory and immune responses, and apoptosis in skin diseases, such as atopic dermatitis. Dysregulated apoptosis is associated with various pathologic conditions, including inflammation and cancer in skin. Polyphenols, including flavonoids and tannins, have been shown to have anti-oxidant, anti-inflammatory and anti-tumor effects. However, the effect of acertannin on TRAIL-induced apoptosis in keratinocytes has not been determined. To assess the preventive effect of acertannin on apoptosis-mediated skin inflammation, we investigated the effect of acertannin on TRAIL-induced apoptosis in human keratinocytes. TRAIL induced nuclear damage, decreased Bid, Bcl-2, Bcl-xL and survivin protein levels, increased Bax levels, induced cytochrome c release, activated caspases (-8, -9 and -3) and increased tumor suppressor p53 levels. Acertannin prevented the TRAIL-induced formation of reactive oxygen/nitrogen species, apoptosis-related protein activation and cell death. The results suggest that acertannin may reduce apoptotic effect of TRAIL on human keratinocytes by suppressing the activation of the caspase-8- and Bid-pathways and the mitochondria-mediated apoptotic pathway, leading to caspase-3 activation. The preventive effect of acertannin on TRAIL-induced apoptosis may be associated with the inhibitory effect on formation of reactive oxygen/nitrogen species. Acertannin may prevent the TRAIL-induced apoptosis-mediated skin inflammation.
Lee
Chung Soo
CS
Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea. leecs@cau.ac.kr
Jang
Eun-Ra
ER
Kim
Yun Jeong
YJ
Seo
Seong Jun
SJ
Choi
Sun Eun
SE
Lee
Min Won
MW
D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004347:Drug Interactions; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects*; D019906:Nuclear Magnetic Resonance, Biomolecular; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D016339:Spectrometry, Mass, Fast Atom Bombardment; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D013634:Tannins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
D061945:Caspase Inhibitors; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D013634:Tannins; D020169:Caspases